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1 



^^^1 31967 

mmmi mimm or hialu 



Ethnopharmacologic Search for 
PSYCHOACTIVE DRUGS 



Within the symbolic chemical representation on the cover 
are shown a view of a mushroom stone from the Namuth 
collection and a morning glory blossom. The mushroom 
stone — early pre-classic, circa B.C. 1000-500 — contains a 
figure believed to be that of a young woman before a metate 
or grinding stone. 



Workshop Series of Pharmacology Section, N.I.M.H. No. 



Ethnopharmacologic Search for 
PSYCHOACTIVE DRUGS 

Proceedings of a Symposium held in San Francisco, California 
January 28-30, 1967 



DANIEL H. EFRON, Editor-in-Chief, 
National Institute of Mental Health, 
Chevy Chase, Maryland 



BO HOLMSTEDT, Co-Editor, NATHAN S. KLINE, Co-Editor, 

Karolinska Institutet, Rockland State Hospital, 

Stockholm, Sweden Orangeburg, New York 



Sponsored by: 

Pharmacology Section, Psychopharmacology Research Branch 
National Institute of Mental Health Public Health Service 
U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE 

1%^ 



The opinions expressed and any conclusions 
drawn are those of the participants of the 
Symposium and are not to he understood as 
necessarily having the endorsement of, or 
representing the viewpoints of, the Public 
Health Service of the U.S. Department of 
Health, Education, and Welfare. 



Public Health Service Publication No. 1645 1967 



For sale by the Superintendent of Documents, U.S. Government Printing Office 
Washington, D.C. 20402 - Price $4.00 



ORGANIZING COMMITTEE 



Daniel H. Efron 
Seymour M. Farber 

Bo HOLMSTEDT 

Nathan S. Kline 
Roger H. L. Wilson 



Pharmacology Section, Psychopharmacology Research 
Branch, National Institute of Mental Health, 
Chevy Chase, Maryland 

Continuing Education in Medicine and Health Sciences, 
San Francisco Medical Center, Univesrsity of California, 
San Tranei'sco, California 

Department of Toxicology, Swedish Medical Research 
Council, Karolinska Institute, Stockholm, Sweden 

Research Center, Rockland State Hospital, 
Orangeburg, New York 

Continuing Education in Medicine and Health Sciences, 
San Francisco Medical Center, University of California, 
San Francisco, California 



CONFERENCE COMMITTEE 



Chairman : Seymour M. Farber Leon Epstein 

Virginia Barrelier Mrs. Bo Holmstedt (Artist) 

Patricia K. Black Bo Holmstedt 

Daniel H. Efron Nathan S. Kline 



Chauncey Leake 
E. Leong Way 
Florence Webster 
Roger H. L. Wilson 



INVITED PARTICIPANTS 



SIRI VON REIS ALTSCHUL 

Botanical Museum of Harvard University, 
Cambridge, Massachusetts 

I. I. BREKHMAN 

Institute of Biologically Active Substances, 
Far-Eastern Branch of Siberian Depart- 
ment of Academy of Sciences, U.S.S.R., 
Vladivostok 22, U.S.S.R. 

JOSEPH P. BUCKLEY 

Department of Pharmacology, School of 
Pharmacy, University of Pittsburgh, Pitts- 
burgh, Pennsylvania 

GBORG E. CRONHEIM 

Riker Laboratories, Inc., Northridge, CJali- 
fomia 

JOHN W. DALY 

Laboratory of Chemistry, National Insti- 
tute of Arthritis and Metabolic Diseases, 
National Institutes of Health, Bethesda, 
Maryland 

VENANOIO DEULOFEU 

Universidad de Buenos Aires, Facultad de 
Ciencias Exactas y Naturales, Parera 77, 
Buenos Aires, Argentina 

DANIEL H. EFRON 
Pharmacology Section, Psychopharmacol- 
ogy Research Branch, National Institute 
of Mental Health, Chevy Chase, Maryland 
CONRAD H. EUGSTBR 
Department of Organic Chemistry, Univer- 
sity of Zurich, Zurich, Switzerland 
OLBLLAN S. FORD 

Department of Anthropology, Yale Univer- 
sity, New Haven, Connecticut 

DANIEL X. FREBDMAN 

Department of Psychiatry, University of 

Chicago, Chicago, Illinois 

CARLETON GAJDUSEK 
National Institute of Neurological Diseases 
and Blindness, National Institutes of 
Health, Bethesda, Maryland 

LOWELL D. HOLMES 

Department of Anthropology, Wichita State 
University, Wichita, Kansas 



BO HOLMSTEDT 

Department of Toxicology, Swedish Medi- 
cal Research Council, Karolinska Insti- 
tutet, Stockholm 60, Sweden 

EVAN C. HORNING 

Lipid Research Center, Department of Bio- 
chemistry, Baylor University College of 
Medicine, Houston, Texas 

HARRIS ISBELL 

Department of Medicine, University of 
Kentucky Medical Center, Lexington, Ken- 
tucky 

NATHAN S. KLINE 

Rockland State Hospital, Orangeburg, New 
York 

MURLE W. KLOHS 

Medicinal Chemistry Section, Riker Labo- 
ratories, Northridge, California 

HANS J. MEYER 

Department of Pharmacology, University of 
Freiburg, Freiburg i. Br., Germany 

OLAUDIO NARANJO 

Bscuela de Medicina, Universidad de Chile, 
Santiago, Chile 
CARL C. PFEIFFER 

Section on Neuropharmacology, New Jer- 
sey Neuropsychiatric Institute, Princeton, 
New Jersey 

EFRlCN CARLOS DEL POZO 

Instituto de Estudios Medicos y Biologicos, 
Universidad Nacional de Mexico, Mexico 
D.F., Mexico 

THORNTON SARGENT 

Donner Laboratory, University of Califor- 
nia, Berkeley, California 

GBORG J. SBITZ 

Koln-Lindenthal, Diirenerstrasse 175, Ger- 
many 

RICHARD E. SCHULTES 

Botanical Museum of Harvard University, 
Cambridge, Massachusetts 

ALEXANDER T. SHULGIN 

Department of Pharmacology, University 
of California, San Francisco Medical Cen- 
ter, San Francisco, California 



vii 



STEPHEN I. SZARA 
Section on PsychopMrmacology, Clinical 
Neuropharmacology Research Center, Na- 
tional Institute of Mental Health, St. Eliza- 
beths Hospital, Washington, District of 
Columbia 

DBRMOT TAYLOR 

Department of Pharmacology, School of 
Medicine, Center for Health Sciences, 
University of California, Los Angeles, 
California 

EDWARD B. TRUITT 

Division of Physiology and Pharmacology, 

Battelle Memorial Institute, Columbus, 

Ohio 



PETER G. WASER 

Department of Pharmacology, University 
of Zurich, Zurich, Switzerland 

S. HENRY WASSfiN 

Gothenburg Ethnographic Museum, Norra 
Hamngaten 12, Gothenburg, Sweden 

R. GORDON WASSON 

Botanical Museum of Harvard University, 

Cambridge, Massachusetts 

ANDREW T. WEIL 

Harvard Medical School, Cambridge, Mas- 
sachusetts (mailing address: 128 Lexing- 
ton Ave., Cambridge, Massachusetts) 



viii 



PREFACE 



The use of plants or tlueir extracts for medicinal or religious cere- 
monial purposes is very old — practically as old as the human race. The in- 
formation about the use of plants as psychotropic agents by man is probably 
found in the Bible. The apple that Adam ate (whatever the variety) could 
be considered as a psycho-energizer. Was it a stimulator, did it enhance 
memory or learning abilities, or did it activiate the desire for acquiring more 
information ? As with our new psychotropic drugs, I don't know if it brought 
happiness and comfort, or new problems, aggravations, and unbappiness. 
Another example of early use and knowledge of medicinal plants we find 
in the fact that the most ancient medical god of Mesopotamia — Sin — was 
also the god of medicinal herbs. 

The development of drug chemistry brought : first, isolation from plants 
of a number of pharmacologically active substances (e.g. curare, atropine 
ouabain, etc.), later, synthesis of these entities and their derivatives; and 
finally, creation of completely new molecules, formerly not known, in the 
plant or animal kingdom. 

We know, also, that in the process of development and worship of chemistry 
we somehow forgot about our prime source, the plants. We forgot that we 
have used only some of the known substances of plant origin. At the same 
time, the intrusions of civilization have been progressively destroying the 
sources of our knowledge, as well as the source itself of many plants — plants 
which are used either in medicine or in ceremonial and sacred context. Today, 
time is running out if we want to save this information, and perhaps use for 
medicinal purposes some of the unknown compounds contained in plants. 

The idea of acquiring knowledge about these plants and compounds we 
have neglected or forgotten was the reason for organizing this symposium. 
It was self-evident that this meeting had to be multidisciplinary. We invited 
pharmacologists, pharmacists, chemists, biochemists, psychiatrists, anthropol- 
ogists, etc., etc. We wanted to exchange existing information, confront dif- 
ferent points of view, and outline and stimulate research objectives for the 
future. 

As one of the organizers of this symposium, I am certainly biased, but 1 
feel that this meeting was very successful. I would like to include here the 
opinion of one of the participants. 

"This," he remarked, "is the first meeting I have attended that at the end 
of the sessions we had as many or even more participants than in the begin- 
ning — this is a measure of the interest the meeting has created." 

We discovered after the meetings how many scattered researchers in wide 
and varied fields could contribute to the knowledge which we seek. This find- 
ing alone was one of the very important immediate gains from the sym- 
posium. And we hope that in the future we will be able to organize a second 

ix 



meeting on the same topics, and cover a much broader spectrum of problems 
in the ethnopharmacologic search for psychoactive drugs. 

The meeting was divided into six sessions, all but the first ending in panel 
discussions. All authors who delivered papers at the session served also as 
panelists. They discussed ditferent problems among themselves and answered 
questions from the floor. The discussion after Session IV covered a special 
topic: "Psychoactive Action of Various Tryptamine Derivatives," and ex- 
perts in this field were invited. The discussions after Sessions V and VI were 
merged, and covered, besides specific topics of these sessions, all problems 
dealt with in the symposium. Speakers from other sessions also participated 
in this dicussion. 

The discussions held after the sessions were recorded m extenso, and are 
printed here following the papers of each session. Because of the multidis- 
ciplinary character of the symposium, problems of terminology and the ex- 
tent of discussion, no restrictions were imposed on participants with regard 
to nomenclature used, order of material or uniformity of presentation and 
reference listing. The diversity of form and style of the various presentations 
was not altered for publication; they remain in their original form. 

We extend our deep appreciation and thanks to the local group from the 
Ck>ntinuing Education in Medicine and Health Sciences, University of Cali- 
fornia, San Francisco Medical Center, for their excellent work in organizing 
this meeting in San Francisco. This group, under the chairmanship of Dean 
Seymour M. Farber, with the participation of Dr. Roger H. Wilson, and 
Mesdames Virginia Barreliei", Patricia K. Black, Florence Webster and 
Matilda Wilson, deserves a great deal of credit for the success of our meeting. 

It would be remiss for me not to remark here (and I am doing so with de- 
light) on the contributions of Drs. Bo Holmstedt and Nathan Kline, co- 
editors of this volume. Without their vision, interest, know-how, persistence 
and scientific knowledge, this meeting could not have taken place. I would 
like also to express my thanks to Dr. Albert A. Manian and Mrs. Shirley 
Maltz from the Pharmacology Section, N.I.M.H., for their help in the 
preparation of this manuscript. 

Finally, many thanks to all speakers, discussants and participants. In final 
analysis, it was their contributions which made the meeting a success, and 
helped so much in the stimulation and delineation of new directions in re- 
search — directions which may bring us a new arsenal of useful drugs, es- 
pecially in the field of psychiatry and neurological diseases. 

D.H.E. 



X 



CONTENTS 



Page 

Organizing Committee v 

Conference Committee v 

List of Invited Participants vii 

Preface ix 

Greetings — ^WUlard C. Fleming xv 

Introduction — Nathan S. Kline xvii 

Letter from A. Hofmann xxi 

SESSION I AN OVERVIEW OF ETHNOPHARMACOLOGY 

Chauncey D. Leake, Chairman 

CHAIRMAN'S INTRODUCTION 1 

Chauncey D. Leake 

HISTORICAL SURVEY 3 

Bo Holmstedt 

THE PLACE OF ETHNOBOTANY IN THE ETHNO- 
PHARMACOLOGIC SEARCH FOR PSYCHOTOMI- 
METIC DRUGS 33 

Richard E. Schultes 

EMPIRICISM AND MAGIC IN AZTEC PHARMA- 
COLOGY 59 

Efren Carlos del Pozo 

PERSPECTIVES ON THE USE AND ABUSE OF PSY- 
CHEDELIC DRUGS 77 

Daniel X. Freedman 

SESSION II PIPER METHYSTICUM (KAVA) 
Georg E. Cronheim, Chairman 

CHAIRMAN'S INTRODUCTION 03 

Georg E. Cronheim 

THE FUNCTION OF KAVA IN MODERN SAMOAN 

CULTURE 107 

LoweU D. Holmes 

RECENT OBSERVATIONS ON THE USE OF KAVA 

IN THE NEW HEBRIDES 119 

Carleton Gajdusek (With an Appendix: Historical and 
Ethnographic Accounts of Kava Usage.) 

CHEMISTRY OF KAVA 126 

Murle W. Klohs 

PHARMACOLOGY OF KAVA 133 

Hans J. Meyer 

xi 



Page 



SESSION II PHARMACOLOGY OF KAVA 141 

Joseph P. Buckley 

ELECTROPHARMACOLOGICAL AND BEHAV- 
IORAL ACTIONS OF KAVA 152 

Atnedeo S. Marrazzi 

EFFECT OF KAVA IN NORMAL SUBJECTS AND 

PATIENTS 155 

Carl C. Pfeiffer 

ETHNOGRAPHICAL ASPECTS OF KAVA 162 

CleUan S. Ford 

DISCUSSION 174 



Chairman — Georg E. Cronheim 
Members of the Panel: 

Joseph P. Buckley 

CleUan S. Ford 

Carleton Gajdusek 

Lowell D. Holmes 

Murle W. Klohs 

Hans J. Meyer 

Carl C. Pfeiffer 

SESSION III MYRISTICA FRAGRANS (NUTMEG) 

Edward B. Truitt, Jr., Chairman 



CHAIRMAN'S INTRODUCTION 185 

Edward B. Truitt, Jr. 

NUTMEG AS A PSYCHOACTIVE DRUG 188 

Andrew T. WeH 

THE CHEMISTRY AND PSYCHOPHARMACOLOGY 
.OF NUTMEG AND OF SEVERAL RELATED 
PHENYLISOPROPYLAMINES 202 

Andrew T. Shulgin, Thornton Sargent and Claudio Naranjo 

THE PHARMACOLOGY OF MYRISTICIN AND 

NUTMEG 215 

Edward B. Truitt, Jr. 

DISCUSSION 223 



Chairman— Edward B. Truitt, Jr. 
Members of the Panel: 

Claudio Naranjo 

Thornton Sargent 

Alexander T. Shulgin 

Andrew T. Weil 

SESSION IV SOUTH AMERICAN SNUFFS 
Bo Holmstedt, Chairman 

ANTHROPOLOGICAL SURVEY OF THE USE OF 

SOUTH AMERICAN SNUFFS 233 

S. Henry Wassen 



xii 



SESSION IV THE BOTANICAL ORIGINS OF SOUTH AMERICAN Page 

SNUFFS 291 

Richard E. Schultes 

VILCA AND ITS USE 307 

Siri von Reis Altschul 

EPENA, THE INTOXICATING SNUFF POWDER OF 
THE WAIKA INDIANS AND THE TUCANO MED- 
ICINE MAN, AGOSTINO 315 

Georg J. Seitz 

CHEMICAL CONSTITUENTS AND PHARMACOL- 
OGY OF SOUTH AMERICAN SNUFFS 339 

Bo Hohnstedt and Jan-Erik Lindgren 

DISCUSSION ON THE PSYCHOACTIVE ACTION 

OF VARIOUS TRYPTAMINE DERIVATIVES 374 

Chairman — Bo Hohnstedt 
Members of the Panel: 

John W. Daly 

Efren Carlos del Pozo 

Evan C. Horning 

Harris IsbeU 

Stephen I. Szara 

SESSION V AYAHUASCA, CAAPI, YAGE 
Daniel H. Efron, Chairman 

PSYCHOTROPIC PROPERTIES OF THE HARMALA 

ALKALOIDS 385 

Claudio Naranio 

THE MAKING OF THE HALLUCINOGENIC DRINK 
FROM BANISTERIOPSIS CUAPI IN NORTHERN 
PERU 392 

Dermot Taylor 

CHEMICAL COMPOUNDS ISOLATED FROM BA- 
NISTERIOPSIS AND RELATED SPECIES 393 

Venancio Deulofeu 

SESSION VI AMANITA MUSCARIA (FLY AGARIC) 

Daniel H. Efron, Chairman 

FLY AGARIC AND MAN 405 

R. Gordon Wasson 

ETHNOPHARMACOLOGICAL INVESTIGATION OF 
SOME PSYCHOACTIVE DRUGS USED BY SIBE- 
RIAN AND FAR-EASTERN MINOR NATIONAL- 
ITIES OF U.S.S.R 415 

I. I. Brekhman 

ISOLATION, STRUCTURE AND SYNTHESES OF 
CENTRAL-ACTIVE COMPOUNDS FROM AMA- 
NITA MUSCARIA (L. ex Fr.) HOOKER 416 

Conrad H. Eugster 



xiii 



Page 

SESSION VI THE PHAKMACOLOGY OF AMANITA MUSCARIA_. 419 
Peter G. Waser 

DISCUSSION 441 

Chairman — Daniel H. Efron 
Members of the Panel: 

Venancio Deulofeu 

Conrad H. Eugster 

Claudio Naranjo 

Dermot Taylor 

Peter G. Waser 

R. Gordon Wasson 
Subject Index 453 



xiv 



GREETINGS 



WiLLARD C. Fleming, D.D.S. Chancellor 

University of California, San Francisco Medical Center, 
San Francisco, California 

My name is Fleming. I am Chancellor of the San Francisco Medical 
Center. If you do not know me, I prefer to introduce myself always, because 
if my friends introduce me I am a little fearful of people I do not know — I 
do a much better job myself. 

I was born some sixty-seven years ago in Sausalito of poor but honest 
parents. The poverty angle must have been a dominant genetic factor because 
my daughter has the same problem. 

I came here as a student of dentistry in 1918. I became a member of the 
Dental Faculty in 1923. I became Dean of the Dental School in 1939. After 
three years of attempting to retire, I took three years to find my successor. 
I thought this was fine, until one of my "friends" said: "Bill, did it ever 
occur to you they don't want to make the same mistake twice ?" 

From there to Dean of Students ; and I have since last July been Chancellor 
of this campus. I have no illusions about why a Chancellor, Mayor or Gover- 
nor gives introductory speeches. This is for the audience to calm down, chat 
with one's neighbor, get the identification, and so on. 

I will follow the same pattern. After residence here of almost fifty years, 
you should understand that the local history of this center is of interest to 
me. History can be a very static chronicle of what has happened ; or on the 
other hand, it can be a very dynamic encounter, and establish a sort of a 
curve of progress that can be extended as a curve of probability into the 
future. 

I welcome the participants of the symposium entitled, "Ethnopharmaco- 
logical Search for Psychoactive Drugs." I have a great deal of difficulty with 
that word. This is really the first time I have gone through it quite smoothly. 

If you agree with what I said about history being used as our prediction 
of events to come, you may agree this campus is historically the logical place 
to sponsor this idea. 

The history of California and in particular the Bay Area, is replete with 
the part medicine has played in its development. Bear Flag Republic ; vigi- 
lante movement in San Francisco ; the role of California in the years of Civil 
War; the bubonic plague epidemic; the Golden Gate Park and the health 
crisis that grew out of the fire and earthquake of 1906 ; an interesting course 
of development. 

At the start of the very facilities that were in here, now, to give you some 
idea of how this started : like some medical schools in the early days, this 
school started with the history of a proprietary school, in other words, a 
school for profit. Then in the Gold Rush days of '49 and '50, a great many 
physicians came to California. They were adventurers, charlatans, and also 



XV 



some very highly qualified and respected professional people. They were in- 
clined to be a quarrelsome lot. This is an attribute that has not quite died 
out yet ; and it is hard to think of another group that was so individualistic. 

Among them was Dr. Hugh Toland, a well trained and well qualified sur- 
geon. He tried his luck in the gold fields, but like so many others shortly 
returned to private practice in San Francisco. He was eminently successful 
both professionally and economically. During the '60's his annual income 
was reported to be over forty thousand dollars — more than they pay the 
Chancellor today. 

This phenomenal income for those days was accomplished by taking ad- 
vantage of two situations: The pioneers of those days were subject to many 
medical conditions and diseases, and of all of these, scurvy and syphilis were 
high on the morbidity list. Like many physicians of those years. Dr. Toland 
compounded and dispensed his own drugs, so it is no surprise to learn that 
in the backroom of Dr. Toland's offices were two barrels. One was labeled 
"Anti-Syph" and the other, "Anti-Scrof". There were no mail order houses, 
but there was the Wells Fargo Express throughout the entire west. 

Through the dispensing of drugs for treatment of syphilis and scurvy 
by mail order, Hugh Toland became wealthy. Like so many people of these 
days, he attempted to memorialize himself by founding a medical school in 
his name. It is an interesting and intriguing story how, with the aid of 
Dr. Richard Beverly Cole, his first Dean of the medical school, this pair 
persuaded Regents of the newly started University of California to take 
on the Toland Medical School as the medical school of the University of 
California. 

The Regents refused to name it Toland School of the University of Cali- 
fornia, but they did agree that there should be a physical part or plant with 
the name of Toland. Thus, today we have in our University of California 
Hospital a small auditorium known as the Toland Auditorium. 

Our Department of Pharmacology has always been strong, as has our 
School of Pharmacy. Possibly it is our heritage, the fact that our medical 
center has a strong pharmacological school here, resting on one barrel of 
Anti-Syph and one barrel of Anti-Scrof. 

At any rate, one can see that this symposium and its participants are in a 
hospitable environment. You are a welcome addition to a long line of 
predecessors, a fair example of the past and a prologue to the future. 

Again I officially welcome you to the opening of this symposium. 



xvi 



INTRODUCTION 



The Psychology, Philosophy, Morality and Legislative 
Control of Drug Usage 
Nathan S. Kline 

Research Center, Rockland State Hospital 
Orangeburg, New York 

Man's Need for Action 

Man is an animal impelled by internal forces to act. Just what form 
that action will take depends on the sensations experienced, the learned 
modifications of innate response patterns, and the possible alternatives exist- 
ing in the immediate environmental situation. Behavior based on purely ra- 
tional decision, if it exists at all, is certainly rare. Action is usually evoked 
by the sensual and emotional, or at times by reflex or even motor needs. 

Provocation& to Action 

Each of us is continuously being teased, hoodwinked, wheedled, invaded, 
bluffed, seduced and assaulted. When such blandishments to action are at the 
cognitive or even the emotional level the attempts are often obvious enough. 
More basic and often underriding them are appeals and approaches to 
primitive patterns of sensation involving incense, drums, drugs, ritualistic 
postures, idols, pageantry; rhythmic sounds and motions interspersed with 
abrupt syncopes; vast or close repetitive visual designs, color shock and most 
of all, movement. There are elusive, lingering, attractive, unidentifiable odors 
or revolting stenches that stir some troubled layer that lies below conscious- 
ness ; and the body itself, the skin with its ceaseless prickling, itching, stretch- 
ing, hotness, coldness never really leaves us alone. Nor do the muscles that pro- 
test by making us fidget if they are not moved frequently and then ache if 
they are exercised too long or too hard ; the vague internal stirrings, appetites, 
"all the nameless feelings that go coursing through our breast." Finally, there 
is the mind's own place, eternally restless, seeking, peeking, poking, squirm- 
ing, probing. Quiet and silence is a kind of death, from which we fear we 
may never be able to rouse ourselves. 

The Role of Drugs in Altering Perception : and the Partial Dependence of 
Such Responses on Environment and Expectation 

Evocation and certainly control of these response patterns is still largely 
"unscientific." Experience and a particular habit of mind are necessary, how- 
ever, before experience can be decocted into an effective guide through these 
mazes. Fatigue, hyperexcitement and drugs, by producing dissociation, tend 

xvii 

262-016 0-67— 2 



both to heighten such experiences but at the same time to break down 
sophisticated self -awareness. 

The loss of ego integrity with its capacity for reality testing leaves the self 
wide and uncritically open to prior expectations and environmental influ- 
ences. How the drug-induced perceptual, kinesthetic or other distortions will 
be interpreted will therefore vary from culture to culture and even from 
individual to individual. Occasionally the same drug may induce profound 
depression, Dionysian ecstasy, terror or bland inditierence. Yet if we induce 
similar expectations and control environment, the response is usually pre- 
dictable. Duration is yet all too short and side effects still all too great, but 
we are well along toward recognizing both the circumstances and the agents 
which will do what we ask of them, by way of temporarily altering the 
perceived universe. 

Society's Moral Attitude 

Whether such para-universes lead to improA^ed philosophic or psychologic 
insights is far from clear. The use of drugs for any thing other than medical 
therapeutic purposes has always been construed as a threat — even when the 
purpose was ostensibly religious — few except the in-group would sanction 
such use. Even at the most simple level there is confusion ; "taking drugs" 
has an immoral connotation despite the fact that the particular drug may be 
life saving; there is only disapproval of escape from intolerable thoughts, 
feelings or situations. At times drugs serve to induce actions which would 
otherwise not be possible; the hope of ex-static (i.e., out of the status quo) 
movement leads man to seize upon whatever is at hand to trv to bring about 
such alterations. "The desire to take pills" wrote Olser, "is the greatest 
feature which distinguishes man from the animals." 

Why the Increased Interest and Use of Drugs at This Time and Place in 
History? 

Here I repeat what I have written elsewhere : 

To varying degrees each of us mortgages the present for the future : we tolerate present 
discomfort in expectation of eventual relief or even reward. Those parts of the remem- 
bered past which make us queasy are usually justified as contributing to some useful 
purpose yet to be realized. In the process we create a cultural as well as a personal his- 
tory involving the whence and hence of existence. 

On rare and glorious occasions some individual or group floods through time with an 
epic tide and in sheer admiration we are all swept along. More frequently the individual 
narrative thread is thin and frayed. In place of the grand patterned fabric we see only 
the thrums of existence. The whole business becomes a drag. Bugged by what we trail 
along and hung up on what is yet to come, we seek temporary or semipermanent escapes. 

Today we lack any viable universally accepted dramatic plot. The success (not the fail- 
ure) of nineteenth century rationalism has left us at least momentarily without a 
denouement. Not that those dated objectives of adequate food, housing and racial equal- 
ity for everyone have been attained but, as in the stock market, their achievement 
has been "discounted" since it is obvious that within another few hundred years they 
will be substantially achieved. The sense of great purpose and broad adventure which 



xviii 



these goals engendered has vanished. Instead of singing down the high road we are 
looking at our sore feet. It requires solid stupidity, bland carelessness or extraordinary 
courage to disregard signposts which say "To Nowhere." The road is studded with squat- 
ters who block those who would pass. The gatherings at the campflres are not for coun- 
sels or imaginative planning but to titillate with pointless ghost stories. 

Curiosity and action are thus directed inward. Drugs that help sever the tenuous 
ties with the outside world become highly prized since they both assist and justify the 
disregard for external realities. . . . 

In the search for new values to give rise to a new narrative the towering, probing 
mystics of the past have sought to recapture the UR-experience upon which every Estab- 
lishment originally drew strength until it became formalized. This invariably demanded 
the shattering of the idols or the escape from the Concept. Visions, iconoclasm, tran- 
scendence took place as the inevitable realization of a whole life's agon. Smashing a few 
clay figures or experiencing visual hallucinations does not produce an Abraham or a St. 
Theresa. Every great mystic has had experiences dissociated from the time and culture 
in which he lived — but the dissociation arose out of inner necessity. Conversion in turn 
is facilitated by the ecstasy of dance, ritual death, drugs. Dissociation per se has no 
value and can become meaningful only as it is integrated into a conceptual framework. 

This incorporation can be strongly directed from outside. . . . 

The dissociation can also produce panic if the attempt is made to retain dissolving 
ego controls. Once these are surrendered a para-infantile acceptance of the universe 
is experienced in which there are no clear ego boundaries so that the One-ness with the 
All comes about. Whether this feeling (or any other) has important value dei)ends 
entirely on how it alters the organization and action of the organism. 

Can We Legislate Control? 

Pharmaceuticals, like firearms, in themselves can be described only by such 
terms as potent or precise. Not their effectiveness but their application deter- 
mines whether they are "^ood" or "bad". We probably should not, and in 
any case can not effectively, legislate against exploration of these other worlds. 
But we must protect ourselves by knowledge of what to expect and by 
attempting to control who may use these agents and for what purposes. There 
will obviously be wide differences of opinion on this score. Past epidemics of 
opiate or of cocaine usage finally required legal restrictions which did serve 
some useful purpose. Attending, or reading the records of, the present sessions 
is an act of affirmation in that they lead to increased understanding. We push 
back the darkness a bit ; the darkness of the mysterious world of drugs and the 
equally dark and mysterious realms of self-knowledge and self-control. 

In addition to moralizing, proselytizing, speculating; new legislation has 
and will continue to emerge in an attempt to influence the natural history 
of this uniquely human venture in which man deliberately alters his experi- 
ences of the world. As to how effective or desirable such legislation has been 
or will be, I can best end with a comment of Ambrose Bierce about Satan : 

Satan made himself multifariously objectionable and was finally expelled from Heaven. 
Half way in his descent he paused, bent his head in thought a moment and at last went 
back. "There is one favor that I should like to ask," he said. 

"Name it." 

"Man, I understand, is about to be created. He will need laws." 

"What, wretch ! You his appointed adversary, charged from the dawn of eternity with 
hatred of his soul — you ask the right to make his laws?" 
"Pardon ; what I have to ask is that he be i)ermitted to make them himself." 

xix 



LETTER 



FROM Albert Hofmann, Ph. D., Pharm. D., H.C. 

Deputy Director Sandoz A. G., 
Basel, Switzerland* 

January 19, 1967 

Mr. Chairman, dear Colleagues, 

While it is undoubtedly possible, with the aid of psychoactive drugs, to 
span both time and space, this method of overcoming these factors is unfor- 
tunately possible only psychically and not physically. Would the latter be 
possible, you may rest assured that I would now have taken the appropriate 
dosage of LSD or psilocybin so as to be transported on the flying carpet to 
San Francisco, for the purpose of participating in the symposium on psycho- 
active drugs. 

I very much regret the fact that, for reasons of company policy, it was 
impossible for me to actively participate in this Congress. It is nonetheless 
my desire to convey from here in Basel, to the numerous prominent research 
workers in the field of psychoactive drugs attending this conference, my best 
wishes and the expression of the hope that the exchange of ideas will be 
fruitful. 

The investigations of the lysergic acid derivatives, from which LSD 
resulted, have continued uninterruptedly in a variety of directions in the 
Sandoz research laboratories. 

Thus, for example, it was possible, in pursuing the serotonin antagonistic 
activity first observed in LSD, to develop new lysergic acid derivatives in 
which a specific serotonin antagonistic activity is of prime importance. One 
of these highly active compounds has been introduced into therapy for the 
interim treatment of migraine. 

In a particular field of research closely related to the theme of this congress 
and initiated by the discovery of LSD, our investigations on psychotomimetic 
drugs have been pursued. In using the experiences gained with LSD as the 
foundation, the problem of the so-called Mexican magic mushrooms, which 
has been studied ethnomycologically by Gordon Wasson and botanically by 
Roger Heim, was solved from a chemical point of view. The active ingre- 
dients, psilocybine and psilocine have been synthesised and made available 
for psychiatric research. The magic mushrooms in turn led us to a further 
important Mexican magic drug, namely Ololiuqui. In the Ololiuqui seeds, 
provided us by Wasson, we found the active ingredients to be lysergic acid 
derivatives, the main components of which are lysergic acid amide and 
lysergic acid hydroxyethylamide. 

It would have given me great pleasure had I been able, at this symposium, 
to discuss in detail this most unusual, one can almost say magic circle of 
research which, starting from lysergic acid amides, namely lysergic acid 

*Dr. Hofmann was unable to attend this meeting and his letter was read to the audience by 
Dr. N. Kline. 

xxi 



diethylamide (LSD), proceeded via two Mexican magic drugs — the sacred 
mushroom "Teonanacatl" and the Morning Glory seeds "Ololiuqui" and led 
back to the lysergic acid amides. I sincerely hope that I shall be able to satisfy 
this desire at the next symposium on psychoactive drugs in the not too distant 
future. 

In conclusion I should like to express a few general points of view on 
psychoactive drugs. 
These drugs are of especial importance in the following three fields: 

1. In neuro- and brain-chemistry they are useful tools for the investiga- 
tion of biochemical processes which form the basis of the nervous and 
psychic functions. 

2. In psychiatry they have proved themselves to be compounds which, 
upon sensible administration, are becoming ever more important 
medical aids in psychoanalysis and psychotherapy. 

3. From a epistemological point of view we must face the consequences 
resulting from the fact that it is possible, with the aid of mere traces 
of a compoimd, to radically affect the psychic processes and mental 
functions. This finding may throw new light on the age-old prc^blem 
of the relationship and interrelationship of body and soul, or more 
generally, of mind and matter. 

To a large extent the non-medical, partially legitimate, partially illegiti- 
mate, interest in and use of hallucinogenics or psychedelics is as a result of 
the possibilities mentioned under 3 above, namely of attaining a profound 
transformation of the conscious with the aid of these drugs. 

It is in fact this very general interest in psychedelics, which has unfortu- 
nately, in some cases, led to dangerous misuse, that behooves scientists to con- 
tinue research in the field of psychoactive compounds in all directions as 
quickly as possible, so as to elucidate the possibilities of these potent drugs in 
order that they may be used for the benefit of mankind. 

It is my fervent wish that, in this respect also, this congress will be 
successful. 



Yours 




xxu 



SESSION I 



AN OVERVIEW OF ETHNOPHARMACOLOGY 



Chauncey D. Leake, Chairman 



I 

Chairman's Introduction 



Chauncey D. Leake 

Department of Pharmacology, University of California 
San Francisco Medical Center, San Francisco, California 

Following the example set by Chancellor Fleming, I suppose I should 
introduce myself. I am Chauncey Leake, and I have little idea exactly why' 
I should be honored by being asked to be the Chairman of this first session. 
I have had some contact with psychoactive drugs, largely through the asso- 
ciation with the late Gordon Alles, who died unfortunately in 1963 at the 
age of sixty-two. He did a great deal of the work on the amphetamines and 
the extraordinary hallucinogenic agents that had been developed in the 
amphetamines in the old pharmacological laboratory that we had over here. 

I did some work on the bufotenine, which, when it is injected, is a tough 
drug to handle. It is difficult to get into solution. I have reported on mush- 
rooms, but they were not hallucinogenic, although it was stated they did cause 
peculiar feeling, but this was due to the agaric acid in them, which has 
a local irritant. 

I am thrilled to see you here, even in the face of the rain. I understand 
pharmacologists are tough and I think psychopharmacologists are especially 
tough, they seem to like this type of weather. It has been this way all across 
the country last week where the pharmacologists have been meeting. 

Our session this afternoon is going to be a good one, and we start appro- 
priately with a consideration of the historical survey of the field of 
ethnopharmacology by Dr. Bo Holmstedt. 



1 



Historical Survey 



Bo HOLMSTEDT 

Department of Toxicology, Swedish Medical Research Council 
Karolinska Institutet, Stockholm, Sweden 



The most fascinating part of ethnopharmacology is perhaps that dealing 
with man's use of intoxicating compounds. A few — not too many — books 
have been written encompassing this subject, the most prominent being Louis 
Lewin's "Fantastica" (Lewin 1924).^ The story of the use of these drugs 
is as old as man himself. Many people have for example speculated over 
what drugs and arrow poisons are mentioned in the Iliad and the Odyssey. 
There is not much need for speculation on this matter since the possible 
alternatives have been thoroughly discussed in the light of the 19th century 
achievement in pharmacology by two such authorities as Oswald Schmiede- 
berg and Louis Lewin. (Schmiedeberg 1918, Lewin 1920) . Likewise, the toxic 
substances used during the middle ages and particularly during the witch 
trials have been much discussed. There is no need to go into this here. 

This review is supposed to cover ethnopharmacology, and there was no 
ethnopharmacology before there was pharmacology. With some exaggera- 
tion it can be said that pharmacology started during the nineteenth century 
independently in three places.^ One was Paris where the work of Magendie 
and his successors paved the way, the second was Edinburgh, where Sir 
Eobert Christison among other things investigated ordeal poisons and coca, 
and advocated the rapid withdrawal in opium addiction. The third place 
was Dorpat, later called Jurjew and Tartu, in Estonia, where pharmacology 
as an academic science started around the middle of the 19th century. Of 
particular interest to the ethnopharmacology of psycho-active agents are 
Paris and Dorpat. This review will deal with some of the men who worked 
at these places. 

Taking for granted that no ethnopharmacology can exist without true 
pharmacology it is appropriate to start this review at the beginning of the 
19th century. At that time, the knowledge of foreign people, their habits, 
food and drugs in Europe and USA was generally speaking negligible. A 
spearhead thrust into this ignorance was Napoleon's ill-fated adventure in 
Egypt. 

Napoleon was a remarkable general in many respects, in this specific case 
because he took with him to Egypt a library and 175 learned men who ob- 
served, wrote down, sketched and collected information about languages, 

♦This Investigation was supported by Grant MH-12007 from the National Institute of Mental 
Health, U.S. Public Health Service, Chevy Chase, Md. 

^ A new print of the original English edition has recently appeared : Phantastica, Narcotic and 
Stimulating Drugs ; Their Use and Abuse, by Louis Lewin, Routledge & Kegan Paul Ltd., London, 
1964. 

Those interested In the history of pharmacology are referred to Readings in Pharmacology by 
Holmstedt and Liljestrand, Pergamon Press 1963. 

3 



archeology and folk lore. This ultimately resulted in the publication of 24 
volumes (Description de I'Egypte) printed between 1809-1813. These books 
stimulated enormously the interest in the Orient and led to a series of travels 
to Egypt, Asia Minor and Africa. Many people published travel accounts, 
such as the French poet and statesman A. de Lamartine (1790-1851), and 
the interpreter of the hieroglyphs, J. F. Champollion (1790-1832). Cham- 
pollion made his expedition to Egypt 1828-1829. 

Of particular importance to psychopharmacology is, however, the travel 
in this part of the world of J. J. Moreau (de Tours), a French psychiatrist 
whose work unfortunately is much forgotten. Moreau and Champollion 
apparently had the same guide or dragoman as it was called at the time 
(Moreau 1841). 

Moreau was the first medical man to work systematically with centrally 
acting compounds. It is therefore appropriate to go into some detail about 
his life and works. 

Jacques-Joseph Moreau {de Tours) was born at Montr6sor (Indre-et Loire) June 3, 
1804. (Baruk 1962 Collet 1962, Ritti 1887). 

His father, a soldier in the armies of the Republic and the Emperor, traversed the 
whole of Europe, taking part in most of the battles and was finally awarded the cross 
of the Legion of Honour. He resigned only after the battle of Waterloo, and spent the 
rest of his life in Belgium, where he devoted all his time to mathematics, for which 
science he had a great passion. 

While the father carried on this turbulent life, the son began his studies of the Classics 
at the college of Chinon, later terminating them at the college of Tours. Thanks to pro- 
found and brilliant studies he passed with success his matriculation examination. 

Moreau then continued his studies at the Medical School, where he was characterised 
as : A zealous and industrious student with a tremendous appetite for learning. The 
Medical School of the public hospital of Tours at that time was run by one of the most 
famous medical men of the period, Bretonneau. Moreau was fortunate in hearing the 
lectures of this teacher. 

After a stay of two years with this master, Moreau went to Paris to complete his 
studies and to take his degree. We are not aware of the circumstances around his appli- 
cation for the position as assistant physician at the Charenton mental hospital, but 
there is no doubt that on July 6, 1826, the date of his nomination, he found the mission 
of his life to which he would devote himself as profit for science. 

At that time the psychiatrist Esquirol had recently become head of the mental hos- 
pital, and thanks to him a number of useful reformations had been introduced for the 
benefit of the patient. Besides his great intelligence Esquirol was no less great as far 
as his character was concerned. The following maxim is ascribed to him "One must 
love the mentally ill in order to be worthy and capable of being of service to him." 

Among the various methods of treatment for the mentally sick — travels — had been 
prescribed even as far back as ancient Greece. Esquirol had a great number of clients — 
people came from all parts of France and even from abroad to consult him. Among 
them were rich persons to whom he could prescribe long travels ; he entrusted them to 
the intelligent care of his young assistants. Also Moreau was commissioned with such 
a task, and visited Switzerland and Italy with a patient. 

Travel then became a necessity for Moreau. He had nothing to keep him in France ; 
he was young and had no desire to settle down. He longed to see foreign countries. 
Esquirol entrusted him with the care of a new patient, this time for a very long absence : 
An absence of three years and a journey to the Orient. To visit the Orient ! What a 
dream for a young man ! And this at a time when eyes were turned towards these sunny 
countries from where came since ten years the most extraordinary news. Each stage 
of the journey would lead him to places where classic events faded in comparison with 



4 



J. J. Moreau (de Tours) 1804-1884 



the more recent ones. One hardly thought of the Pharaohs when setting foot on the soil 
of Egypt, governed by the famous Mohammed All. When passing through Asia Minor 
interest was less lively for the rapid campaign of Alexander the Great than for the 
exploits of Ibraham-Pasha and his 30,000 Egyptians, the victories of whom had dis- 
turbed the Sultan's power. 

The young and enthusiastic Moreau wished to learn and profit as much 
as possible from what he saw and heard, and for this reason he adopted the 
dress and the customs of the countries he passed through. He wrote down 
what he experienced, and it is much to be regretted that he never published 
his observations. Some of them are, however, contained in his medical books. 

It is striking that in the Orient the mentally ill appear to be fewer than 
in Europe. Is this marked difference to be explained by climate, race, or by 
the political and religious institutions? Moreau adhered to the opinion of 
Montesquieu, who admitted the joint responsibility of these various causes : 

The heat of the climate can be so excessive that all strength leaves the body. The 
lacli of strength passes on to the spirit — no curiosity, no noble sentiments, no generous 
feelings .... laziness is happiness .... resignation. . . . 

Immediately upon his return to Paris, Moreau hastened to renew his old 
acquaintances and acquire new ones. He met Esquirol again and his circle 



5 



of disciples among whom he counted numerous friends. The master received 
him with open arms : he bestowed on this dear pupil the tokens of his aSec- 
tionate benevolence, and eased for him his first entry into the medical career, 
always difficult in Paris. 

During his stay in the Orient, Moreau had noted the common use of 
hashish, especially among the Arabs. He must also have tried it himself 
since in his travel reports he writes rather lyrically about "pleasures im- 
possible to interpret" which this "marvellous substance" brings about, and 
which "would be impossible to describe to anybody who had not experienced 
it". Thanks to a mysterious legend and particularly to the imagination of 
poets and novelists, only the wonderful effects of this substance were known. 
Moreau wished to contrast poetry with observation and experience, and his 
experimental research into the psychopharmacological actions of the extract 
of Indian hemp permitted him to throw light on psychological phenomena 
which had previously been obscure. They inspired him also with ingenious 
ideas on the nature of insanity. 

Xo criticism can be made of his investigative procedures. Moreau took 
hashish himself. Thanks to the singular property of the substance t-o keep 
intact "consciousness and the innermost feeling" of the user, he could 
analyze all his impressions and in a way be aware of the disorganization 
of all his mental faculties. In order to complete this internal observation 
of himself, he also commissioned the persons surroundina: him to note 
carefully his words, acts, gestures and the expression of his face. The results 
were very characteristic. They fully justified the name of "fantasia" which 
the Oriental imagination gives to the intoxication with Kief, one of the 
many names for hashish. Moreau desired, moreover, "controls with other 
people." He turned to his pupils and with enthusiastic curiosity they lent 
themselves to experiments with hashish in the most varying doses, giving 
exact accounts of what they experienced. Moreau observed with scrupulous 
care every (external) symptom during the course of intoxication. The two 
series were compared and full conformity was proved. 

The effect of the hashish reveals itself by a series of intellectual disturb- 
ances, Moreau described all the sensations with meticulous care. 

In 1845 Moreau published his extensive book of more than 400 pages 
entitled Du Hachich et de I'alienation mentale (Hashish and mental illness) . 
Its detailed accounts of the hashish intoxication aroused the interest of 
numerous physicians and the curiosity of many writers, and was followed 
by a great deal of personal experimentation. Moreau's book gave rise to 
the modem researches regarding the effects of hashish, and can also be held 
responsible for its use in certain Paris circles in the middle of the 19th 
century. However, it never became a true epidemic in all parts of Europe, 
confining itself mainly to the Near and Middle East. 

Such factors as origin, education and environment as well as the atmos- 
phere in which hashish is consumed, affects individuals in different ways. 
Due to the great number and varying nature of the psychic effects of the 
hashish intoxication, these cannot be outlined in the same way as the 



6 



physical effects. However, Moreau enumerated eight main groups of symp- 
toms. They are: 

(1) General feeling of pleasure. 

(2) Increased excitement combined with a heightening of all senses. 

(3) Distortion of the dimension of space and time (generally a mag- 
nification of the actual dimensions : Minutes are changed into days 
or years, inches into feet, etc.). 

(4) A keener hearing combined with a great susceptibility to music and 
the phenomenon that ordinary noise is enjoyed as though it soimded 
sweet. 

(5) There often arise persistent ideas on the verge of persecution 
mania. 

(6) Disturbances of the emotions, mostly in the form of an increase 
of already existing feeling. 

(7) Irresistible impulses. 

(8) Illusions and hallucinations of which evidently only the first 
named are related to objects of the exterior world. 

Moreau pointed out that psychiatry could profit from these experi- 
ments by comparing the symptoms to those in mentally ill people. The illu- 
sions produced by the hashish — are they not attacks of insanity? These 
attacks will take on all the characteristics of violent insanity if only the 
dose of the toxic agent is increased. Moreau had the occasion of sadly ex- 
periencing this. His assistant in pharmacy wished to see the effects of the 
Indian hemp when taken in a larger quantity, and swallowed 16 grams of 
the extract. 

A very intense delirium broke out, followed by agitation, incoherence and 
hallucinations of all kinds. Three days passed before the young man re- 
gained his ordinary calmness and the entire use of his power of reasoning. 
During the course of the attack he maintained, however, some idea of 
what was happening to him. 

Moreau postulated that there exists in insanity a primary factor which 
is the source of all symptoms; i.e., excitation, which is the primitive genera- 
tive power. He attached special importance to this hypothesis, and considered 
it as equal to other great scientific laws. Moreau also compared insanity with 
dreams. The hypothesis is not new; it already preoccupied Aristotle. The 
learned philosopher from Stagira writes in his books on "Dreams" that "the 
reason why we, even awake, deceive ourselves in certain illnesses is the 
same which produces in us, in our sleep, an impression of a dream." The 
favorite formula of Moreau was: "Insanity is the dream of the man who 
is awake." 

Even though Moreau cannot be said to be dependent on his countryman 
the French materialist and medical man La Mettrie (1709-1751) who said: 
"Man is what he eats", he still considered a range of causes for insanity. 
With regard to the conception of an organic origin he writes: "I am not 
against the conceptions of organic damage but I require to see the lesion : I 
only believe in damages which are proven, not in those that are supposed 



7 



Dll HACHISCH 

ET I)E 

L'ALIENATION MENTALK 

ETUDES PSYCHOLOGIQIIES 

PAR 

J. MOREAl ^ 

1 I>E TOURS ) , 

'liiispiic di" Ricctrc. Mrmlur *lc Ih Sin irtr 
oi k-nUiti* lie l*;iri.*!. 



PAULS. 

I.I i; II \ I 111 j: Dh; I'OU i i n. m v.sson i i c". 

i'i.Ai:i i>K I. Li;i>i.i,~iii';-Mi:iii.i 1 M I 

to exist."' This certainly was a veiy wise position to take. Even in our days, 
organic or biochemical lesions in mental illness have been difficult to prove. 

Moreau loved art in all its forms. He gladly sought the company of 
writere and artists. His works on hashish had j)ut him in contact with nu- 
merous poets and novelists and he was well acquainted with Balzac, Grerard 
de Nerval and Theophile Gautier. The author of "la comedie humaine" 
wrote him the day after a "fantasia" a'bout an idea that he had had for 
twenty years: "To make a new brain in an idiot (with the aid of hashish) 




8 



in order to see if the mind could be expanded by development of the rudi- 
ments." It has a familiar ring. 

Moreau passed away June 26, 1884, at the age of 80 after a short illness. 
He was undoubtedly the first psychiatrist with interest in psychopharma- 
cology. It seems that during his life time he was never recognized as he 
should have been. Among those who did not understand his qualities Avas 
regretfully Frangois Magendie (Collet 1962). On the other hand, Claude 
Bernard once called hashish a psychopharmacological counterpart of cu- 
rare. Up to recent years, however, with regard to hashish people have 
been mostly interested in the literary feats of Theophile Gautier and Charles 
Baudelaire, and "Le Club des Haschischins" with its strange meeting in the 
old hotel on He St. Louis in Paris. It is perhaps typical that a very recent 
collection of papers around the subject hashish only mentions Moreau in 
passing. (Solomon Ed. 1966.) 

Unlike Moreau Ernst von Bihra (1806-1878), was the prototype of a 
wealthy, private scientist. Although he acquired academic degrees he per- 
formed a good deal of his research in his own house. 

Bibra was born in Unterfranken, studied in Wiirzburg, where he became 
M.D. and Ph. D. and later partly in Niirnberg living on his estate Schweb- 
heim. He was mostly interested in chemistry, but also was a geographer and 
a numismatologist (Giinther 1901). Of special importance to this account 
is his trip to South America 1849-1850. He was more or less forced to 
leave for political reasons, because of his liberal attitude during the revo- 
lution in 1848. 

The most important result of this journey — except for his travel ac- 
count ("Reise in Siid-Amerika, B. Mannheim, 1854") which is well worth 
reading — -is the book "Die narkotischen Genussmittel mid der Mensch" 
(Niirnberg 1855). The book was undoubtedly prompted by his South Amer- 
ican trip, and is the first of its kind to summarize the effect of centrally 
acting compounds, in all seventeen. He devotes chapters both to compounds 
such as coffee and tea, and also to Amanita Muscaria, opium, hashish and 
coca, the chewing of which he had I'ich opportunities to observe during his 
trip to South America. Due to the fact that comparatively little was known 
about these drugs at the time, Bibra's book created quite a sensation. He 
did not pursue this line of research, but devoted the rest of his life to his 
private hobbies, such as numismatics and writing of novels. 

There were other people who were to make such compilations during the 
nineteenth century. One of them was Georg Noel Dragendorff (1836-1898). 

Dragendorff was born in Rostock, Germany, as the son of a medical man, studied 
cliemistry in Heidelberg and learned thie trade of pharmacy in his home town (Hart- 
wich 1897-1898). His main interest was chemistry. The famous Witte pharmacy in 
his home town soon expanded into a house of medicinal chemistry and Dragendorff 
became employed there. He heard lectures by Bunsen, Kirchhoff, Helmholtz and Brlen- 
meyer, but it is said that he never had an opportunity to hear a lecture in pharma- 
cognosy either in Rostock or Heidelberg. The first one he ever heard was the one he 
had to give himself when he had become professor in Dorpat. 

In 1862 Dragendorff was called to St. Petersburg to help organize the editing of a 
journal of pharmacy. He learned to speak Russian and also helped organize the pharma- 
cies in Russia. From St. Petersburg he was called to become professor of pharmacy 

9 

262-016 0-67— 3 



and director of the Pharmaceutical Institute of Dorpat, 18&4. Dorpat came to be his 
home for 30 years, and when he finally resigned his chair in 1894 he returned to his 
home town of Rostock, where he organized a private laboratory and carried on research 
until his death. 

Dragendorff's work dealt with two things: one, relevant to the present 
account, was the chemical investigation of plants; the other was toxicologi- 
cal analysis. He was particularly interested in the medicinal plants used 
by foreign people, and had acquired collections from far off countries in 
his institute at Dorpat. His most famous work and a summary of his activi- 
ties in the field, was published shortly after his death and is now a rare book : 
"Die Heilpflanzen der verschiedenen Volker unci Zeiten", 1898.^ With regard 
to his chemical activities we only have to point out that he had numerous 
pupils from many countries, and that no reputable phytochemist is unfa- 
miliar with Dragendorff's reagent for alkaloids. 

Another German pharmacist who perhaps accumulated even greater 
knowledge in one field of ethno-pharmacology was Carl Hartioicli (1851- 
1917). (Schroterl9l7.) 

Hartwich was born in Tangermiinde where his father had a pharmacy, the manage- 
ment of which the son took over in 1879. He was, however, so interested in scientific 
activities that he sold the pharmacy and moved to Braunschweig. From there he went 
to Bern in order to take his doctor's degree and then again to Braunschweig to become 
university lecturer in pharmacy and pharmacognosy. A few weeks afterwards (also 
in Hartwich's case before he had given one single lecture) he accepted a call to the 
Swiss Polytechnical Institute in Ziirich. He began his service in the autumn of 1892 
and stayed for 24 years, as professor and head of the Pharmacology Department. 

Hartwich published a multitude of papers dealing with numerous drugs and stimu- 
lants. In these studies the historical and ethnographical questions are strongly empha- 
sized. Of a particularly historical interest is "Die Bedeutung der Entdeckung von 
Amerika f iir die Drogenkunde" ( 1892 ) . 

Hartwich's most important publication, however, is "Die menschlichen 
Genussmittel", 877 pages with 24 tables and 168 pictures in the text (1911). 
He worked on this monumental volume during a decade, with considerable 
joy and even with the passion of a fanatic collector. The gigantic quantity 
of material is astounding and includes drawings, photographs, observations 
of his own, and literary notes from the most remote sources. The physical, 
historical, ethnographical and commercial and ethical aspects of the com- 
pounds are treated with the same love. The richly decorated book is a true 
gold mine of information that was previously widely dispersed. 

In addition to these voluminous collections of ethno-pharmacological and 
ethno-botanical material there arose during the second part of the 19th 
century the science of psychology. The pioneers in this field were Hennann 
V. Helmholtz (1821-1894), Gustav Theodm^ Fechner (1801-1887) and Wil- 
helm M. W. Wundt (1832-1920). 

The foremost service of W. Wundt to psychology was the introduction 
of laboratory investigation. Before his time experimental research in psy- 
chology had been mainly individual. He gathered around him enthusiastic 

^ At the time of writing a reprint of the original has been issued. 

Georg Dragendorff, Die Heilpflanzen der verschiedenen Volker and Zeiten, Neudnick der Ausgabe 
Stuttgart 1898. Antiquariat Fritsch, Postach 1043, 79/Ulni/ Do. Germany. 



10 



students and assistants whom he trained in the methods of exact experi- 
mentation. The first real institute for psychological studies was erected by 
Wundt in Leipzig 1879 (Kraepelin 1920). It consisted of two rooms and 
some tables with equipment, some of which was Wundt's personal property. 
No grant for equipment was available and Kraepelin tells how it had to be 
made by hand from wood, tin, strings and cardboard. They had, however, 
accumulators and chronoscopes. In spite of the obvious poverty the new 
institute was filled with a pioneering spirit and enthusiasm. 

Wundt had never had near contact with psychiatry or drug research even 
though he had to do with it now and then. One of his first pupils was 
Emil Kraepelin (1856-1926). 

Kraepelin was born in Neu-Strelitz (Mecklenburg-Strelitz) , studied in Leipzig and 
Wiirzlburg with the intention at the very start to become a psychiatrist. He graduated 
in 1878 and came to the Munich Mental Hospital. In 1882 he became, assistant of 
Flechsig in Leipzig, but soon left in order to work in the Institute of Wundt. At 
the start working with experimental psychology, he later turned wholly to clinical 
psychiatry which he endeavored to put on a new basis that brought world-wide fame 
to his Munich Olinic. 

Kraepelin published the first account on the use of the new psychological methods 
in clinical pharmacology which he undertook during his tenure of a professorship in 
Dorpat (188&-1890). In that remarkable university at this time worked also not only 
Dragendorff but Rudolf Kobert, who held the chair in pharmacology. Obviously, 
Kobert was the one who interested Kraepelin in applying his psychological tools to 
the study of drug effects in man (Jelliffe 1931). Among the drugs he studied were 
morphine and alcohol, and after he had left Dorpat this resulted in the first real 
monograph of psycho-pharmacology where the new methods were applied : "Ueber 
die Beeinfliissung einfacher psychischer Vorgange durch einige Arzneimittel — Jena, 
1892." 

Kraepelin maintained a lifelong interest in the pharmacology of alcohol. In his hospital 
he introduced variously colored lemonades immediately christened "Kraepelin liquors" 
(KoUe 1956). 

Robert's association with the clinic of psychiatry in the meantime had resulted in 
the publication of another epoch-making paper, written together with one of 
Kraepelin's co-workers (Kobert R. and A. Sohrt: "Ueber die Wirkung des salzauren 
Hyoscin,"1887.). 

Rudolf Koiert (1854^1918) started his medical career in Halle under Theodor 
Weber and spent many years as assistant to Schmiedeberg before he was called upon to 
become H. H. Meyer's successor at the famous department of pharmacology in Dorpat 
(Sieburg 1919). He remained in Dorpat until 1897. The title of his chair was Pharma- 
cology and Physiological Chemistry; he was also a teacher in History of Medicine 
and Pharmacy. In 1899 Kobert became professor at the university of Rostock where 
he remained until his death. 

From Kobert's hand originate a great many publications concerning pharma- 
codynamics and toxicology. He wrote a textbook in toxicology which has had a con- 
siderable influence on many fields Including forensic medicine. He was one of the 
two great toxicologists of the nineteenth century, the other being Louis Lewin. The 
great learning and wide scope of his interest is witnessed among other things by 
the issue during his time in Dorpat of "Historische Studien aus dem Pharmakologischen 
Institut". This work in five volumes is an invaluable source, among other things for 
information to early research of drugs, also to research of drugs affecting the central 
nervous system. 

The above mentioned paper by Kobert and Sohrt is of considerable psycho- 
pharmacological interest. For the first time here, dissimilarities and sim- 



11 




Emil Kraepelin 1856-1926 



12 



ilarities between atropine and scopolamine are pointed out, the latter com- 
pound at this time called hyoscine. Robert and Sohrt in their carefully 
conducted investigation demonstrated the sedative action of the latter com- 
pound. The experiments were made both on animals and man, and included 
a series of self -experiments. Robert writes the following: 

. . . During the past autumn vacation I had the opportunity to arrange at the 
Department of Psychiatry in Dorpat and supervise directly an investigation of the 
actions of a pharmacological agent. This investigation, which lasted several months, 
was undertaken because work on animals is of value If it is extended to man. The 
pharmacological agent involved was hyoscine. 

. . . Mr. Sohrt, the assistant in the Department of Psychiatry, wrote up these experi- 
ments at my instigation for his inaugural thesis. In view of its limited circulation I 
wish to present here the following account taken from the thesis: 

. . . Sohrt gave himself at 10.04 p.m. an injection of 0.5 mg hyoscine hydrochloride. 
The pulse rate before injection was 64 per minute. After a latent period of 10 minutes 
Sohrt observed as the first symptom a ptosis which made it diflScult for him to keep 
his eyes open. Gradually a feeling of heaviness mthout headache occurred. His head 
tended to drop to his shoulders and it became diflScult to keep the head upright. His 
limbs felt as if they were lumps of lead attached to the body. There was a marked 
tiredness. 

Throughout this period S. was fully conscious and able to give an account of 
everything and to answer questions speedily. He was able to read his own writing 
without much difficulty and did not feel sick. At 11.25 p.m. he stood up, but his walk 
was unsteady. He went to bed, therefore, and at once fell asleep. He had a quiet 
sleep without dreams. On the following morning S. woke up at 9 a.m., instead of at 
5 or 6 a.m., which was his usual time. His head felt slightly numb, but this symptom 
disapi)eared after breakfast. 

These experiments show that hyoscine, 0.5 to 1 mg, given subcutaneously, produces 
in healthy man dryness of the mouth, dilation of the pupils, marked sleepiness and 
tiredness, but is devoid of other special actions. 

... In nearly all those cases of illness which are associated with a state of 
excitation hyoscine produced sleep promptly or at the very least induced sedation, 
even when all other drugs used for this purpose failed to produce an effect. 

By far the most interesting personality of all psychopharmacologists of 
this time Avas Louis Lewin (1850-1929) . 

Lewin was born in the small town of Tuchel in Western Prussia. In 1854 he came 
to Berlin where he remained more or less until the end of his life. He graduated from 
the University of Berlin. In 1875 as an M.D., he studied for a while with Pettenkofer and 
Voit in Munich, and became "Privatdozent" in pharmacology in Berlin in 1881. In 1894 
he became titular professor at the University of Berlin but held no full academic posi- 
tion. Only as late as 1919 did he become permanent honorary professor at the Technical 
Academy. There has been much speculation about the reasons why Lewin did not ad- 
vance academically in pharmacology and toxicology, and it has been said that he could 
have become head of the greatest pharmacology department in Germany had he re- 
nounced his Jewish faith and consented to become baptized. Whatever truth there may 
be in this, he established his own private laboratory and lecture hall in No. 3 Ziegel- 
strasse in an old tenement house in the centre of the medical district of Berlin. He 
preferred to teach and to do his research with his own means in these surroundings. 
Financially, he was partly enabled to do so through the fact that although he had no 
official position, the courts preferred him to all other experts in Germany in toxicology 
and industrial hygiene. 

Lewin's way of lecturing was extraordinary and held the audiences spellbound. It 
has been said that he expounded facts with a contagious enthusiasm and performed his 



13 



Ueber die Beeinflnssimg 
einfacher psychischer VorgaBge 

durcli einige Arzneimittel. 

Experimentelle Untersuehungen 

von 

Dr. Emil Kraepelin, 

ProfeeBor der Pa v c- b i a t r i c in fl e i d e 1 ber g. 

Mit einer ('Urventafel. 



Jena, 

Verlag von Gustav Fischer. 
1892. 



experiments with loving care. Any narrow specialization was foreign to him. He could 
quote flawlessly in foreign languages, and marshal facts from all four corners of the 
world and all periods of history. Classical and contemporary authors were all familiar 
to him. Many famous men who visited his lectures were deeply influenced by him. Among 
them was J. J. Abel who has been called the father of American pharmacology. Lewin's 
outstanding wide general knowledge meant that he had many friends among scholars 
in other faculties. 



14 



Among Lewin's personal acquaintances were the explorer Georg Schweinfurth, and 
Albert Einstein. In history, geography and anthropology his knowledge was enormous ; 
he showed special interest in travel and topography. It is said that scarcely a travel 
book of importance was unknown to him. His own travelling included visits, among 
other places, to the United States, Switzerland and Italy. 

When surveying Lewin's works one is greatly helped by a list he compiled himself 
before his death. The list includes 248 major publications in the years 1874-1929. From 
the list are excluded book reviews, printed discussions and other minor communications 
of his which were also numerous. Among the publications there are about a dozen books 
and monographs. Lewin himself claimed that by 1880 he had already decided to devote 
most of his time to the side effects of drugs. 

Lewin's first major work, in 1881, "Nebenwirkungen der Arzneimittel", Pharmakolo- 
gisch-klin. Handbuch (Berlin, A. Hirschwald), dealt with this topic and became a classic 
and the first of its kind. This book had two more editions and was translated into three 
languages, including English. Notable among the other books are his outstanding text- 
book in toxicology, a summary of all available knowledge of arrow poisons, two volumes 
on the effects of drugs on the eye, and another work in which he gives the world's his- 
tory as seen by a toxicologist, "Die Gifte in der Weltgeschichte" (J. Springer, Berlin 
1920) . 

It is not possible here to summarize all the fields of interest to which Lewin 
made original contributions, but it is appropriate to dwell on his activities in 
psychopharmacology, a topic in which he published some 20 articles. His 
own contributions to the field occurred mostly in the 1880's. Then he more 
or less left this field, but in 1924 summarized admirably his own work and 
those of others in the first edition of his book "Phantastica". The long delay 
certainly did not mean that he remained unfamiliar with the progress in 
the field; on the contrary, the books show that he kept up to date with all 
achievements made. 

Lewin's first publication, in 1874, was a study of chronic morphinism, 
which he was one of the first to investigate scientifically. In 1886 there ap- 
peared his monograph on Piper methysticum (Kawa Kawa) : "Ueber Piper 
raethysticum (Kawa)." (Monographie. Berlin. A. Hirschwald). This is a 
very comprehensive review of all aspects of the use of Piper methysticvsm and 
current research on its constituents and their chemistry, pharmacology and 
clinical effects. This admirable monograph is now understandably much out 
of date in its chemistry and pharmacology, but it was a pioneering work, 
and the period following its appearance saw the first real progress being 
made in the chemistry of kaava. In 1889 appeared another similar mono- 
graph: "Ueber Areca Catechu, Chavica Betle und das Betelkauen." (Mono- 
graphie. Stuttgart. F. Enke) an equally comprehensive review. 

Before that, however, Lewin had had occasion to get into polemics with 
Sigmund Freud about coca and cocaine. This strange episode in the history 
of science runs as follows : 

A century ago the height of nationalistic pride was to have a man-of-war 
circumnavigate the globe. Austria, a sea power in those days, planned to 
send the Novara on such a trip. Prof. Wohler of Gottingen just before de- 
parture requested the naturalists on the expedition to bring him back a suffi- 
cient quantity of coca leaves to carry out a thorough investigation. Dr. 
Scherzer, one of the scientists, did manage to get some 30 lbs. of leaves to 



15 




Louis Lewin (1850-1929). Picture taken about the time of his trip to the United States. 



16 



Prof. Wohler. His assistant, Niemann, succeeded in isolating an unusual 
crystalline organic base. 

The first description of cocaine occurs in Tagesber. allgem. med. Zentral- 
Zeitung, 25 April 1860, p. 262-263. It is noted that, "It would seem that Coca 
will be of great use to the medicine of the future. ... It has the remarkable 
action on the nerves of the tongue that after a few moments the place of 
contact becomes anaesthetized and almost insensitive". In 1859 Paolo Man- 
tegazza's description of the therapeutic versatility of coca aroused much in- 
terest but little confidence, although subsequently his reports have been largely 
verified. However, early investigations in Austria, Germany and England 
were largely negative in their findings, and by the 1870s there was general 
disillusionment. 

A military surgeon, Aschenbrandt, in 1883 claimed a remarkable effect 
of cocaine upon Bavarian soldiers enabling them to better endure hunger, 
strain, fatigue and heavy burdens. He anticipated a demand of today's purists 
in experimental design by adding the cocaine to the drinking water and not 
telling the soldiers. Unfortunately the use of control subjects was overlooked 
and Aschenbrandt was anything but unbiased. Palmer (1880) in the Louis- 
ville Medical News, and Bentley in the Detroit Therapeutic Gazette (1880) , 
had described the use of coca in the treatment of morphinism. The Louisville 
Medical News said in its editorial comment "one feels like trying coca with 
or without the opium habit. A harmless remedy for the blues is imperial." 

In 1884 Sigmund Freud wrote to his fiancee that he had been experimenting 
with "a magical drug". After dazzling success in treatment of a case of gas- 
tric catarrh he continues "If it goes well I will write an essay on it and I 
expect it will win its place in therapeutics by the side of morphium, and 
superior to it. ... I take very small does of it regularly against depression 
and against indigestion, and with , the most brilliant success." He urged his 
fiancee, his sisters, his colleagues, and his friends to try it (Jones 1956) . That 
same year he published an article "Uber Coca" which among other virtues 
extolled the drug as a safe exliilarant which he himself used and recom- 
mended as a treatment for morphine addiction. For emphasis he stated, in 
italics, that "Inebriate asylums can be entirely dispensed with" and a cure 
effected in 10 days. That same fateful year he used it -for this purpose in 
treating his close friend, Ernst Fleischl. For a while the treatment succeeded 
but increasingly larger doses were needed. Freud spent one frightful night 
nursing Fleischl through an episode of cocaine psychosis and thereafter was 
bitterly against drugs, rarely permitting them even for himself during op- 
erations for the painful carcinoma of the jaw which finally killed him. 

Freud's paper on Coca Avas subjected to a severe criticism by Louis Lewin 
(1885). Among other things, he said: 

I want to state explicitly that according to all available evidence coca is no substitute 
for morphine and that a morphine addiction cannot be cured by the use of coca. . . . 

I am convinced that coca cannot be a substitute for morphine for any length of time 
since the real morphine addict wants the specific morphine effect and since he can very 
well distinguish the euphoria of other substances. Such an exchange does not suit his 



17 



Uebcr 



PIPER METIIYSTICUM 

(KAWA). 

XJntersiiclivingeii 

Ton 

Dr. L. Lewin, 

Decent der t'lLarin:iLologie in dcr Uiiiveriitit Berlin. 



Mit 1 litbograpliiiten Tafel. 



Berlin 1886. 

Verlag von August Hirschwald. 

N\V. Uoler dru Linden 68. 



special needs. The morphinist wants more than the euphoria which can be brought about 
in normal man and which Freud experienced himself when taking 0.05-0.1 gr. cocaine 
hydrochloride. 

However, even if it were possible to treat a morphine addict for a time exclusively 
with cocaine and even if he were given very large doses producing hallucinations and 
a pleasant sopor, there would very likely occur a case of what I would like to call double 
addiction. The man in question would use cocaine in addition to morphine in the same 
way as many morphine addicts use chloroform, chloralhydrate, ether, etc. 



18 



Lewin's clear perception of tliis question was corroborated by A. Erlen- 
meyer slightly afterwards, and also by others. Lewin never understood Sig- 
mund Freud, especially not his psychoanalytical works, and used to refer 
to him as "Joseph der Traumdeuter" ("Joseph, the dream interpreter"). 

In 1887 Lewin made a cross coimtry trip in the US and Canada. According^ 
to some lines in his travel accomat he had thought about emigration. He 
traveled together with one Mr. Jolm Warburg whom he called uncle. His wife 
had grown up in the Warburg family in Hamburg. Other members of this 
family were famous botanists. Lewin's trip across the country resulted in a 
hand-written manuscript of more than 300 pages Avith numerous photos, 
illustrations and cuttings glued into it. It is a family property never printed 
and not intended to be.* It was written as a gift to his wife and given to her 
upon his return to Berlin. The manuscript is a treasure of wealth of informa- 
tion about the US about 1880. Lewin's itinerary took him also into Canada, 
to the big lakes, to San Francisco, Detroit, Washington and back His deter- 
mined way of travelling is well borne out in what he says about his stay in 
San Francisco: 

My main purpose in visiting San Francisco had been to see for myself "Chinatown", 
as the Chinese quarter is called, and esi)ecially the smoking of opium. In our hotel we 
asked for a guide. It appeared that we could get one for 10 dollars — 40 mark. What 
an insolent overcharge ! We asked in a ticket-oflSce — the same charge, hut with a reduc- 
tion to half the price for a guided tour in the daytime. But during the day there Is 
nothing to see there and everybody can then walk through the quarter and the shops. 
I decided to show those swindling yankees that we were able to find the right way by 
ourselves. We asked a policeman what to do to get a policeman as guide. He directed us 
to the main police-station. There I explained my request after having shown my card. 
When the captain began long deliberations with someone else I showed him the legitima- 
tion I had received from Washington. This proved effective. We were to meet our police- 
guide at 9 o'clock in the evening at the station. We told this to Mr. H. who wanted to see 
Chinatown too. Strange to say — the better society of San Francisco does not know it. 
On the way we passed the stock-exchange and went in. After a few paces we meet the 
strapping policeman, our companion for the excursion. After a short time we arrived. 
How many different impressions do I bring home from this visit ! From the moment we 
entered this quarter in which approximately 30,000 Chinese live till we left it, an 
unpleasant odour did not leave us. It is impossible to describe it, it is so repugnant 
that even uncle was, at the beginning, somewhat repelled and disgusted. The streets 
were repulsively dirty and filthy. People throw everything in the streets to let it rot 
there. It is impossible to use the so-called sidewalks, partly because they are full of 
baskets and boxes, partly because there yawn everywhere cellar-holes one might easily 
fall into. I had to roll up my trousers. What a contrast to this filth, when we entered the 
first shop, a barber-shop! There two Chinese were sitting, under the hands of the 
barbers. They had just finished shaving the hair from the forehead to the top, and were 
occupied in tidying the ears and the noses of their clients with very small knives — not 
wider than a straw — and very fine sponges with handles. The barbers removed all hair 
and other substances. On the other side of the street there was a food-shop. 

The streets are dark, lighted only by the shops and by candles burning in the street 
in front of the houses. Every few paces 6-8 wax-candles are stuck into the ground. 
These candles bum down very quickly, but their long stem consists of incense, so that 
there are hundreds of incense-candles fuming in the streets. Asia in America ! What a 
contrast of customs and habits ! But that was not yet the worst by far. We entered a 

* The author wishes to express his gratitude to Mrs. Irene Sachs, N.Y., for permission to publish 
part of the travel account and to Mrs. Hertha Jaff€ and Mr. Mordechai YafE4, Israel, for help with 
the translation. 



19 



... -JS-i- 



L',-'":::!.. ^... ^^j- ^ 

.... „..^„ 




V-a- 



rr 



11 

! — 



^ rr: 



^^""-jf-*. ^ .j-.t^ .c^ —t/^ , 

„W. -Z-i^.^ vOy^w <,-^f..^i, -.^■...-y..-,, .•..-..y- 



.1 



Pages from Louis Lewin's travel account related to visit to Chinatown in San Francisco. 



pitch-dark house — or so it appeared to us as we went in, for we had to light up the 
entrance with matches. By and by we could see some light in the passage we were 
standing in. We were in the only house built in Chinese fashion. I am not expert 
enough to describe it to you as it really is or to make a drawing of it. Perhaps you will 
get some idea? I sketch it as follows. As far as I could see there are 2-3 such stories, 
a cellar-story, the groundfloor and one above. I might be mistaken as to dimensions and 
numbers of rooms but the arrangement in the plan is correct. I sketched it from 
memory while travelling through the State of Colorado. I must explain the broad dark 
areas. These are apertures leading to the cellar. There are corresponding apertures in 
the first story, I think for illumination. If I remember right, there is a banister on 
one side. 

We lighted our way down the stairs leading to the courtyard and to the cellar-story. 
Darkness enveloped us. Our guide opened a door with a glass-window — all the doors have 
a window like this — through which a faint light was glimmering. What we could see was 
interesting to me, but in general an unpleasant view. In a small room, less than two arm- 
lengths long and wide, we saw plank-beds all around leaving only very little free space 
in the center of the room. On one of these I discovered a crouching figure holding an 
opium pipe and inhaling deeply the pernicious fume. Before bim burned the small oil- 
lamp for the preparation of the opium-pill. Such a pill, even a bigger one, is, as I saw, 
enough for 2-3 draughts, seldom four. The extract of opium has an almost honeylike 
consistence. With a very fine metal-spatula — I have a similar one — he takes a small 
amount of the extract and puts it somewhere at the clay-top of his pipe. He then again 
takes the opium up, this time with the needle-like other end of the spatula, passes it 
lightly through the flame to condense it and make it more malleable and tries by turning 
the needle round and round to give the opium pill a cylindrical form. After passing the 
material another two or three times through the flame the desired form is achieved. He 
sticks the needle into the aperture of the pipebowl and, while drawing it back, he 
presses the small cylinder of opium into the aperture of the bowl with his index-finger. 



20 



Now he puts his mouth to the pipe-stem and sucks deeply, deeply, while letting the 
opium-cylinder evaporate near the lamp — it looks for all the world like a thirsty man 
putting his pint-glass to his lips and emptying it in deep endless draughts. After approxi- 
mately half a minute he exhales the fumes which in the meantime have been partly 
absorbed through the mucous membranes of the lungs. This same procedure occurs 
6, 8, 10 times and even more until the gratification of the opium-visions provide the 
compensation for the troublesome preparations. He feels himself transplanted from his 
wretched surroundings. He sees palaces, riches, opulent repasts, splendid garments, 
beautiful amorous women and perhaps oflScies, titles and decorations descending upon 
him. In the morning he awakes — on a straw-mat or a heap of rags in a lightless hole 
filled with pestilential air. Again he trudges by daylight to the hole where he lives. Who 
can blame this human being — with his low grade of education, deprived of moral sup- 
port — if he returns again and again to the pleasurable world of the opium-vision at 
night? 

Again we enter a house, going along what seem still narrower passages. You feel your 
heart beating at the thought of a sudden conflagration. Not the most precipitous point of 
the Canadian Pacific Railway gave me so much fright : The feeling of being shut-in in 
these i)assages nearly choked me ! 

Lewin also managed during the same trip to visit the stockmarket, Chinese 
restaurants and theatres, the house of the Salvation army, and another house 
from which he fled in Victorian dismay. 

However interested Lewin may have been in San Francisco's China Town 
and the smoking of opium, the city he really longed to visit was Detroit. He 
arrived there on September 16, 1887: 

My first errand was, of course, a visit to Parke Davis. We drove along a splendid wide 
avenue bordered by residences with beautiful gardens. Soon we were marvelling at a 
grand extensive building adorned with sand-stone. This building which belongs to the 
company, is not yet fully finished. We enter the oflBce where there work well over fifty 
book-keepers, male and female, cashiers, clerks, stenographers etc. Mr. Wetzell showed 
us round the factory and the printing-shop — I had not expected such a magnitude and 
such a skilled exactitude of workmanship. It is impossible to enumerate all particulars 
to you. Summing up, I can only tell you that the different departments are exemplary, 
from the preparation of juices and extract, the extraction of drugs, bottling, labeling, 
the homogenization of plants to the manufacture of pilular mass, sugaring and coating 
of piUs etc., etc. ... In short, the manufacture of pharmaceutical preparations is worthy 
of the American genius for machinery and for exactitude and cleanliness of use. What- 
ever I received — preparations drugs etc. — you will see for yourself when everything 
arrives in Berlin. 

Among these things he carried back with him to Berlin from Parke Davis 
Co. was Peyotl, the "Mescal buttons". We know this exactly because he has 
stated himself that he got it from the Parke Davis and Co. during his Ameri- 
can trip. He was not long in investigating its properties and there appeared 
in Schmiedeberg's archives and the Detroit Therapeutic Gazette the first ac- 
counts of the pharmacologic properties of Peyotl (Lewin 1888). He says in 
his summary: 

It has toeen proven for the first time that a cactus can possess an extraordinarily high 
toxicity. It will now be appropriate to elucidate the chemistry of this Anhalonium and 
then go further with the investigation of other species of Anhalonium. One must, how- 
ever, also investigate to what purpose and to what extent these Muscal huttons (Sic I) 
are used as stimulants. In a not too distant future I hope to be able to give evidence 
ahout this. 



21 



For some reason he never did, although, he wrote in 1894 a second long 
article on what was then called "Anhalonium Lewinii and other cactea" 
(Lewin 1894). By then, however, Arthur Heffter had already started his 
work on the active principles in the mescaline cactus. 

ArtJmr Heffter (1860-1925) was bom in Leipzig and representative of the 
old German school of pharmacologists with a thorough chemical backgromad 
and a medical training. (Straub 1921, Heubner 1925, Joachimoglu 1960) . He 
worked for some years in agricultural chemistry and then switched to study 
medicine in Leipzig, at the same time working in the laboratory of K. Bohm. 
His habilitation took place in 1892, after which he for some time worked 
under Schmiedeberg in Strassburg. Later he held positions in various uni- 
versities, Leipzig, Bern, Marburg, and finally in 1908 became Liebreich's 
successor at the department of pharmacology, University of Berlin, where 
he held the chair until liis death. 

Heffter 's research activities covered a wide scope of topics. As lecturer he 
was, however, to say the least, mediocre. 

Lewin did not like Heffter and Heffter did not like him. They had very different 
opinions on many things — this concerned particularly Anhalonium Lewinii (Peyotl) on 
which Heffter also had done work. It was a priority comi)etition hetween the two. I 
don't remember it exactly, but I have the feeling that it was something of the sort. Lewin 
was more the artist and interested in the social implications of these substances. 
Heffter was not very verbal, awkward, frankly in the presentation of his material. On 
the other hand, here was this tremendously stimulating, flamboyant orator Lewin who 
carried away his audience with his enthusiasm. The atmosphere fused into the most 
extraordinary experience every time we went to that place to listen to his lecture, and 
you did that in spite of the fact that you didn't have to — it was enough had you followed 
only Heffter's lectures. I went to Heffter's lectures, of course, and I was bored. Lewin 
lectured the first time and I was captured — I went there every time. (Krayer 1963) . 

Heffter proceeded systematically to find the psychoactive principle in 
Peyotl by working it up into chemical fractions and testing these on himself 
in heroic self experiments, much the same way as Albert Hofmami later did 
with psilocybine. It is psycho-pharmacologically interesting to see what kind 
of wonderful visions an obviously dry man like Heffter got out of mescaline. 
Here is his account of the first experiment carried out with pure mescaline in 
man, in 1897 : 

Violet and green spots appear on the paper during reading. When the eyes are kept 
shut the following visions occur. At first there are violet and green spots which are not 
well defined, then come visions of carpet patterns, ribbed vaulting, etc. From time to 
time single dots with the most brilliant colours float across the field of vision. The 
phenomena are generally not as clear as those in the two preceding exi)eriments. Later 
on landscapes, halls, achitectural scenes (e.g. pillars decorated with flowers) also appear. 
The visions can be observed until about 5 :30 p.m. Nausea and dizziness are at times very 
distressing. The appreciation of time is reduced during the first hours of the afternoon. 
In the evening well-being and api)etite are undisturbed and there is no sign of 
sleeplessness. 

The results described above show that mescaline is exclusively responsible for the 
major symptoms of peyote {tnescal) poisoning. This applies especially to the unique 
visions. The experiment performed on 23rd November shows that mescaline hydro- 
chloride, 0.15 g, produces a pattern of symptoms which differs in only a few respects 
from the one obtained with the drug. Both mescaline and the crude drug produced 



22 



bradycardia, pupillary dilatation, headache, dizziness, clumsiness of limb movements, loss 
of appreciation of time, and, what is most important, characteristic visions. 

An attempt to discuss the action of mescaline in detail would not accomplish anything 
in view of the limited number of experimental data, but physiologists and experimental 
psychologists should find work in this field rewarding. It is very likely that we are 
dealing with an action on the central nervous system, although excitation of the periph- 
eral visual apparatus can not be excluded. In this connection I would like to mention 
that Privatdocent Dr. Krdckmann, the first assistant to the Ophthalmological Depart- 
ment in Leipzig, kindly examined me when I carried out the experiment on November 23. 
He was unahle to find any reduction of the visual field either in general or in relation to 
colours. 

At the present moment I would like to leave open the question of whether or not any 
of the peyote (mescal) alkaloids has a therapeutic value. As far as mescaline is con- 
cerned the answer is probably no. Weir-Mitchell and Ellis believe that peyote (mescal) 
will also become popular amongst cultured people as an intoxicating drug. I think that 
this is unlikely because the results which I obtained on myself show that the side- 
effects are so pronounced that they considerably spoil the appreciation of the beautiful 
visions. 

The discoveries of Lewin and Heffter excited a lively interest in the appli- 
cation of the drug in man. Lewin's pupil, Beringer, carried out numerous 
experiments in man with mescaline. 

Kurt Beringer (1893-1949) was born in Uelilingen (Schwarzwald) as the 
son in a peasant family (Jung 1949, Ruffin 1950). In 1911-1914 he studied 
medicine in Heidelberg, and in 1918 he took part in the war as assistant 
doctor. In 1921 he became attached to the Heidelberg Psychiatric and Neuro- 
logical Clinic of Wilmanns, where he stayed for 12 years. In 1928 he took 
part in an expedition to Mongolia. In 1934 he came to Freiburg, where he 
stayed for the rest of his life. 

Among many papers, Beringer published one regarding hashish intoxica- 
tion: "Zur Klinik des Haschischrausches" (1932), and two papers on super- 
stition: "Hexen- und Aberglauben im Schwarzwald" (1938), and "Formen 
des Aberglaubens in Schwarzwald" (1938). These papers bear witness to his 
interest in ethno-pharmacology. His magnum opus, however, is "Der Meska- 
linrausch" (1927), translated into Spanish but never into English. This book 
is to mescaline what Moreau's book is to hashish. It gives a clear cut descrip- 
tion of the psychic and somatic symptoms, and should be consulted by who- 
ever is interested in the actions of mescaline. 

A renewed interest in psychopharmacology was awakened in Germany 
around 1928. It was at this time that Lewin and others became interested in 
the properties of the South American vine Banisteria Caapi. 

On the 13th of February, 1929, Louis Lewin and Paul Schuster gave a 
paper at the Berlin Medical Association. They described the action of 
Banisterin prepared from Banisteria and later proved to be identical to 
harmine in experiments both in animals and man (Lewin and Schuster 1929) . 
At this time they had only 1.2 g of the drug, of which they had given 0.02- 
0.04 g to 18 cases of Parkinsonism. The side-effects were reported to be a 
slight nausea, paleness, tremor and bradycardia. A quarter of an hour after 
the injection the patients had a feeling of being able to move more easily, even 
in difficult cases with contractures. An improvement was reported of, among 
other things, swallowing, chewing, speech, eating, movements of the arms and 



23 



Beitrage zur Giftkunde 

Herausgegeben von 

Professor Dr. Louis Lewin 



Heft 3 

Banisteria Caapi 
ein neues Rauschgift und 

Heilmittel 

von 

Prof. Dr. Louis Lewin 
Mit 2 Karten 




19 2 9 

Verlag von Georg Stiike / Berlin 



24 



walking. They observed a lessening of muscular rigidity. The improvement 
lasted 2-6 hours, occasionally seven days. 

It is remarkable that at this time a film of the action of the drug in three 
patients was shown. This undoubtedly constitutes the first documentation of 
the action of monoamineoxidase inhibitors. Lewin pointed out that the drug 
always affected the ability to move, and seemed inactive psychically. Their 
demonstration raised a tremendous interest, and the popular press took up 
the question of this so called "magic drug". Louis Lewin, sick and old at the 
time, managed to complete a monograph on the subject before he passed 
away: "Banisteria Caapi, ein neues Rauschgift und Heilmittel" (1929). 

In the same year Beringer gave a review of the clinical papers where 
harmine had been used up till then. He also had occasion to comment upon 
its pharmacodynamics, and deplored the inaccurate knowledge of how the 
drug worked. The following sentences are perhaps prophetic : 

First of all it is necessary to find out liow it affects the central nervous system ; 
whetlier this is due to a direct action upon certain centers of the "brain or indirectly 
through the autonomic nervous system througli a change of metabolism. Many things 
speak in favour of the latter explanation. 




Kurt Beringer (1893-1949) 

25 



262-016 0-67— 4 



Beringer also commented that new experiments in his clinic showed that 
the action was not limited to the extrapyramidal system. In his review he 
pointed out that no differences could be found between banisterine and 
harmine. It seems at this time that all research workers considered harmine 
as a new drug for the symptomatic treatment of certain extrapyramidal dis- 
eases, and that in many cases it did more than previously known drugs. It 
proved useful, especially, in the cases of postencephalitic Parkinsonim that 
were prevalent at the time. Some patients had been on the medication con- 
tinually for more than a year without decrease in drug effect. The treatment 
was in no way incompatible with previously used drugs, such as scopolamine. 

The most remarkable account from this time is perhaps the description of 
the self experiments by Z. Halpern (1930 a and b). Dr. Halpern gave her- 
self doses of up to 0.04 g per os and 0.03 g subcutaneously. The action Avas 
sudden, and she had an immediate impression of excitement, with difficulty 
remaining in one place to continue her intellectual labor. Unrest was the 
dominant symptom at smaller doses. All actions were felt as if they were more 
easily done. No euphoria and no clouding of the senses was observed. These 
symptoms Dr. Halpern explained as stimulation of the cortex : 

In all probability, harmine acts ui)on the motor system as a central cortico-motor 
regulation as a stimulating agent acts upon the motor neurons, physiologically to in- 
crease excitation. By higher doses, this excitation was increased even in a belligerent 
way : The author, who normally is not belligerent, has herself experienced this dis- 
charge of the motor functions. The subject started a fight with a man in the street, 
where she was the one who attacked, even though according to the circumstances the 
prospect for the attacker was very unfavorable. 

The consciousness was in no way influenced and in no way abnormal, but the impres- 
sion was felt as if the consciousness was packed in ether. An increased concentration 
of observance was felt. When lying on a sofa, the lightness increased to a feeling of 
a fleeting sensation, and the weight of the body was subjectively less. These clinical 
observations should be compared to the state of levitation frequently reported to occur 
with the crude drug ayahuasca or caapi. 

Dr. Halpern continued her studies in Parkinson patients, and pointed 
out the differences in action between scopolamine and harmine and the 
duality of Parkinson's disease. As is now well known, the monoamineoxidase 
inhibiting property of the harmala alkaloid was found as late as 1958 by 
Udenfriend. 

The enthusiasm for the harmala alkaloids vanished temporarily during the 
thirties, as did much of the interest in ethnopharmacology. A few people, 
however, worked remotely and undisturbed by the rising tide of synthetic 
chemicals and the general lack of interest in exotic poisons. Among them 
Avas Blasius Paul Reko, more commonly known as Bias Pablo Reko. 

Bias Pablo Reko (187&-1953) was born in Prerau, Austria (Cook de Leonard 1955- 
1956). His mother came from Czechoslovakia. Under the influence of his grandfather 
he decided to study medicine at the University of Vienna, where he graduated in 1901. 
From the year 1903 he dwelled in America, first in Chicago, in 1907 in Guayaquil 
Ecuador, and finally in Mexico City. It would seem that he came to Mexico in 1911. 
He lived no less than 15 years in Oaxaca where he worked professionally for some 
mining companies. It was during this time that he became interested in the local 



26 



flora, especially medicinal plants. His interest in this field was combined with ethno- 
graphical and etymological studies. He published many articles in "El Mexico Antiguo" 
about the flora of Oaxaca. He became interested in astromythology through his interest 
in ethno-botanics. 

Reko said himself that he published his papers only to satisfy his per- 
sonal taste. This concerns perhaps mostly his numerological work. To the 
present reader, his ethno-botanical papers seem to be of special importance. 
He was a good botanical observer and had a large collection of indigenous 
plants, among them the magic mushroom used by the Mazatecs. His studies 
were summarized in "Mitobotanica Zapoteca", Mexico, 1945. 

In Jan. 1937 Reko wrote the following letter to Henry Wassen, anthro- 
pologist and curator of the ethnographical museum, Gothenburg, Sweden: 

Jan. 31, 1937. 
Gelati 15, Tacubaya, D.F., Mexico 

Mr. Henry Wassen 
Goteborgs Museum 
Goteborg, Sweden 
My dear Mr. Wassen : 

. . . Apparently you confound me with my cousin Victor A. Reko, the author 
of "Magische Gifte", a journalistic piece of work, by the way, which you need not 
to take very seriously, since its author is neither a botanist nor has he any personal 
experience with the drugs described, most of which he has not even seen and would 
not recognize if he saw them. It is a cleverly made up mi<ctum compositum of compiled 
facts and wild inventions of his own fancy, intended for popular consumation. 

I have deep interest in the work of Prof. Santesson and would like to come in touch 
with him, as I can furnish him some very important botanical materials, awaiting the 
solution of their mystery by a competent chemist. I am forwarding to your direction a 
sample of the "Piule" seed, together with an article of mine on this topic (published in 
1920 and reprinted in El. Mex. Ant. 1934) in the hope that Prof. Santesson might 
get interested in the problem and conduct some experiments in that line. 

"Very likely I get this year also specimen of the Teonanacatl, still used for religious 
rites in some secluded places, but so far never identified . . . 
With best regards 
Yours truly 

Dr. B. P. Reko. 

Both the Piule-Ololiuqui and the Teonanacatl did arrive. 

Carl Gustaf Santeswn (1862-1939) definitely has a place in ethno-pharma- 
cology. He was professor of pharmocology in Stockholm from 1895 to 1927, 
and had studied both with Bohm in Leipzig and with Schmiedeberg in 
Strassburg. (Liljestrand 1939). These teachers influenced his interest in, 
among other things, the study of compounds such as strychnine, strophan- 
thine and curare. He published about 20 papers on arrow poisons, collected 
from all parts of the world. Especially important, however, is the work he 
carried out after retirement. The Mexican drugs he obtained were investi- 
gated and the results published in journals that are not easily found nowa- 
days (Santesson 1937, 1938). Among them were Ololiuqui and Teonanacatl, 
the magic mushroom of Mexico, subsequently investigated by Wasson, Heim 
and Hofmann. Santesson did not have much of the latter, but succeeded 
in carrying out animal experiments with Ololiuqui. It is to the credit of 



27 



Santesson that he was able to notice the central action of this drug in 

animals, and that in his paper he writes : 

In some way the animals had lost their initiative. It seems to me that there is a 
a partial paralysis of the brain, a kind of narcosis ... in these animals there is a 
certain central depression without any other obvious symptoms. 

He concludes his paper by saying : 

The drug deserves a thorough investigation which can only be done with a larger 
supply of material. 

With Santesson's papers expire the old pre- World War II activities in the 
ethno-pharmacologic search for psychoactive drugs. The revival was to come 
about ten years later. 

A cknowledgment 

This work has been supported by a grant from the National Institute of Mental 
Health, Bethesda, USA (MH 12007) and by a grant from the Swedish Medical Research 
Council. 




28 



Plasius Paul (Bias Pablo) Reko 1876-1953. 



Carl Gustaf Santesson (1862-1939) 



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31 



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32 



The Place of Ethnobotany in 
the Ethnopharmacologic Search 
for Psychotomimetic Drugs 



Richard Evans Schultes 

Botanical Museum of Harvard University, Cambridge, Massachusetts 



Page 



Introduction 

Ethnobotany and the Search for New Drugs 

Consideration of Pressing Problems 

Guidlines for the Future 

Bibliography 



33 
34 
37 
55 
55 



Introduction 



The very descriptive word etJmohotany has been defined in sundry ways 
in the 70 years since it was created and first used by Harshberger {23). 
Although Harshberger indicated how ethnobotanical investigation could 
be integrated into overall research, he failed to offer a definition of his new 
term. 

Years earlier, in 1874, Powers {38) had used the term aboriginal totany 
to refer to a study of "all the forms of the vegetable world which the ab- 
origines used for medicine, food, textile, fabrics, ornaments, etc." 

It was, apparently, not until 1916 that a truly broad concept emerged 
that went beyond mere identification and cataloguing of plants used by 
primitive peoples. This broad definition of the term ethnobotany., now rather 
widely held, was promulgated by Bobbins, Harrington and Freire-Marreco 
(4^), and, in effect, attributes to this discipline a study and evaluation of 
the knowledge of all phases of plant life amongst primitive societies, and 
of the effects of the vegetal environment upon the life, customs, beliefs and 
history of the peoples of such societies. 

Jones {27) has offered the following precise definition: "the study of the 
interrelations of primitive man and plants." It is interesting to note that 
Jones and others {9) prefer to restrict ethnobotany to man in primitive states 
of culture. While this premise may and probably does almost always obtain, 
there is really no reason to circumscribe the term in this way. Vestal and 
Schultes {62) looked upon ethnobotany as a part of economic botany. Since 
I do not hold that ethnobotany need be limited exclusively to man in primi- 
tive society, my own definition {Jf.6) circumscribes ethnobotany as "a study 
of the relationships between man and his ambient vegetation." 



33 



Ethnobotany and the Search for New Drugs 



It is natural that an interdisciplinary §eld such as etlinobotany be replete 
with problems for investigation. These are and have been not only numerous 
but varied as well, and the burgeoning nomenclature bears witness to this 
variation. In recent years, such terms as archaeoethnohotany ^ ethnomycology^ 
ethnoecology and ethnopharmacology have been proposed and have come 
into use. 

Nowhere perhaps have the potentialities of ethnobotanical investigation 
been more scintillating than in the search for new psychotomimetic drugs 
{57) . These potentialities have been realized in the case of a number of new 
and previously known hallucinogens that are now relatively well understood : 
the narcotic mushrooms and morning glories of Mexico; the ayahuasca- 
caapi-yaje complex of South America ; the intoxicating snuffs of the Orinoco 
and Amazon basins. They remain to tantalise us, however, in the case of 
several narcotics known vaguely from common names or from sketchy reports 
of travellers and missionaries : several South American snuffs ; the marari 
of lowland Bolivia; an intoxicating "tree-fungus" of the Yurimagua Indians 
of eastern Peru ; the yurema root infusion of the Pankararu of Brazil ; the 
magic woi of the Yekwana of southern Venezuela. Furthermore, they chal- 
lenge us to find, through ethnobotanical avenues, new psychotropic plants 
that most certainly are still in use, but which have never been seen nor re- 
ported by the prying inquisitiveness of man outside of the culture that 
employs the narcotics. 

I cannot help thinking that Linneaus himself must have had ethnobotany 
in mind, at least in part, when he in 1754 wrote in a museum catalogue the 
following philosophy : "Man, ever desirous of knowledge, has already ex- 
plored many things; but more and greater still remain concealed; perhaps 
reserved for distant generations, who shall . . . make many discoveries for 
the pleasure and convenience of life. Prosperity shall see its increasing 
Musuems, and the knowledge of the Divine Wisdom, flourish together ; and at 
the same time all the practical sciences . . . shall be enriched ; for we cannot 
avoid thinking, that what we know of the Divine works are much fewer than 
those of which we are ignorant." 

In the search for new hallucinogens, we have much to do and little time 
in which to do it. Peoples in primitive societies, because they live most in- 
timately with their irmnediate vegetational environment, do possess a valu- 
able understanding of the properties of plants, even though their knowledge 
of plants has sometimes been optimistically exaggerated by both lay en- 
thusiasts and ethnopharmacological zealots. The aborigines' knowledge and 
understanding, furthermore, is probably everywhere far from complete. It, 
therefore, behooves all of us interested in a search for new psychotomimetic 
drugs to carry out our investigations along several avenues of approach, not 
following the ethnobotanical avenue to the exclusion of others {52). It is, 
however, the place of ethnobotany in this search that I shall here discuss, 
and I want merely, at the very start, to put it thus into proper perspective. 



34 



Civilization is closing in on many, if not on most, parts of the world still 
sacred to the less advanced cultures. It has long been pressing in, but its pace 
is now accelerated as the result of geographically extensive wars, extended 
commercial interests, increased missionary activity, widening tourism. 
Modem methods of travel and penetration have given civilisation the tools 
for this accomplishment. Road-building programmes in Latin America pro- 
vide us with but one example of how fast this penetration of the hinterlands 
is proceeding. 

Our great concern lies in the progressive divorcement of man in primitive 
societies from dependence upon his immediate environment. I have often 
stated that perhaps the greatest enemy or, at least, competitor, of ethnophar- 
machological research is the arrival and cheap availability of the aspirin pill. 
More than once this has initiated an astonishingly rapid disintegration of 
native medical lore. I doubt that social scientists are fully aware of the 
rapidity of this disintegration, but the ethnobotanist cannot fail to see it. 
That the aspirin (meaning, of course, modern medicines in general) may be 
more beneficial than herbs and magic is not ours to consider here. What does 
interest us academically and practically is how to salvage some of the medico- 
botanical lore of primitive cultures before it shall have been forever entombed 
with the culture that gave it birth {51). 

In considering the ethnobotanical approach in our search for new drugs 
we must constantly bear in mind the widespread exaggeration of the useful- 
ness of ethnobotanical data. Although we cannot afford to pre- judge reports 
of aboriginal uses of plants simply because they seem to fall beyond the limits 
of credence, we must nevertheless ever keep in mind that there is no reason 
to presume that, because man in primitive living does have knowledge as yet 
unknown to us, he may possess anything more than a limited intuition into 
the properties of plants. 

Although now at long last there is more agreement concerning the larger 
aims of ethnopharmacological investigations, the field has suffered— as has 
ethnobotany in general — from lack of orientation and integration. Ethno- 
botanical research has often, of necessity, been done as a sideline by botanists 
untrained in ethnology ; by anthropologists lacking any knowledge of biol- 
ogy ; or even by laymen, dedicated enough, but devoid of preparation in both 
biology and anthropology. And in more recent years, the training commensu- 
rate with thorough ethnobotanical investigations has enlarged its scope to 
include some familiarity with topics such as chemotaxonomy, which once 
would never have been considered germane. As a result of this checkered 
history, ethnobotanical research, its purposes and its potentialities has too 
often suffered from smug depreciation at the hands of specialists in disciplines 
that have been academically more clearly delimited. 

The potentialities of ethnobotanical research into folk medicine are far 
too extensive for proper treatment in a short lecture, but certain salient points 
may and should be made, and these points may be supported by specific ex- 
amples. In delving into the medicine of primitive societies, we must never 
lose sight of the vast difference between "medicine" in our sense and that in 
primitive societies. In almost all, if not all, primitive cultures, the concept 



35 



of sickness and even of death from natural causes is unknown or incompre- 
hensible. Instead — and we must here over-simplify the problem for our pur- 
poses — supernatural spirits or forces of evil work in sundry ways to bring 
about the impairment of health or cessation of life. We should realize that 
hexing and witchcraft were widely accepted as recently as three centuries 
ago in what was, in many respects, the advanced culture of Europe. Amongst 
the members of primitive cultures to-day, treatment usually comprises various 
kinds of exorcism; and diagnosis, and often treatment itself, must be carried 
out through communication with the spirit or supernatural world. Many 
ways of communicating have been developed, but the employment of vision- 
producing narcotics or hallucinogens of plant origin seems to have been 
widespread in both time and space, and to have occurred in many wholly 
unrelated cultures. 

We do not know exactly how many species of plants there are. There may 
be as many as 800,000. Estimates for the Angiosperms alone vary from the 
usually cited 200,000 to about half a million (55). 

It is interesting to compare the number of species of plants that man has 
found valuable for nutrition with those that he has employed to induce 
hallucinations. Of this vast assemblage of Angiosperms, only about 3000 are 
known to have been used directly as human food. The number of species that 
actually feed mankind is, however, very small. Only about 150 Angiosperms 
are important enough as foods to enter the world's commerce. Of these, only 
12 or 13 stand, in effect, between the world's population and starvation, and 
these dozen or so plants are all cultivated species (55) . 

We find, likewise, that the number of species providing man with narcotic 
agents is very small. Between four and five thousand species are now known 
to be alkaloidal,^ and we must realise that constituents other than alkaloids — 
glycosides, resins, essential oils and others — may also be responsible for nar- 
cotic activity. Probably no more than 60 species, including Cryptogams and 
Phanerogams, are employed in primitive and advanced cultures for their 
intoxicating effects. Of these, only about 20 may be considered of major im- 
portance. What is even more significant is that so few — coca, opium poppy, 
hemp, tobacco — are numbered amongst the world's commercially important 
cultivated plants. Four of these five, if not all five, species are cultigens, 
unknown in the wild state. This bespeaks long association with man and his 
agricultural practices (S5). 

It may likewise be of significance that, whether because of cultural dif- 
ferences or floristic peculiarities or for some other as yet unappreciated 
reason, the New World is much richer in narcotic plants than the Old. These 
statistics, naturally, relate merely to those plants the narcotic properties of 
which man has discovered in his trial and error experimentation during the 
course of human history. The longer I consider this question, the more I am 
convinced that there may exist in the world's flora an appreciable number 
of such plants not yet uncovered by the experimenting natives and still to be 
found by the enquiring phytochemist. This is an aspect of the problem in 
which ethnobotanical approaches cannot help, but even though our etlmo- 

* R. F. Raffauf, personal communication. 



36 



botanical research into narcotic plants is still embryonic, we know enough 
to realise that both the Old and the New Worlds offer rich fields for potential 
discoveries. 

Where do some of the ethnopharmacological problems in connexion with 
our search for new and interesting psychotomimetic agents lie? Let us 
contemplate some of the hints that might guide such research in the future. 

Geographically, the problems may be found almost throughout the globe, 
concentrated, to be sure, in areas where primitive societies still hold sway 
unmolested by the inroads of modern civilisation. 

Consideration of Pressing Problems 

Some of the most interesting enigmas lurk in the desert stretches of 
northern Mexico, where what we might term the "prototype" of the New 
World hallucinogens — peyote or Lofhophora WUUamsii — has long been the 
centre of religious and curative rites in the Tarahumare and Huichol country. 
Peyote, of course, is well known from many aspects, and 13 alkaloids have 
thus far been isolated from it (33) . The explorer Carl Lumholtz (3^) men- 
tioned, however, other narcotic cactus plants, some of which are as yet not 
even botanically identified. "High mental qualities," he wrote, "are ascribed 
especially to all species of Mammilaria and Echinocactus, small cacti, for 
which a regular cult is instituted. The Tarahumares designate several as 
hikuli, though the name belongs properly only to the kind most commonly 
used by them . . . The principal kinds are . . . Lophophora Williamsii. 
The Tarahumares speak of them as the superior hikuli (hikuli waname) . . . 
Besides hikuli waname . . . , the Tarahumares know and worship the fol- 
lowing varieties: 1. Mulato [Mammilari micromeris) . This is believed to 
make the eyes large and clear to see sorcerers, to prolong life and to give speed 
to the runners. 2. Rosapara. This is only a more advanced vegetative stage 
of the preceding species — ^though it looks quite different, being white and 
spiny. 3. Sunami. {Mammilari fissurata). It is rare, but it is believed to be 
even more powerful than waname and is used in the same way as the latter ; 
the drink produced from it is also strongly intoxicating. ... 4. Hikuli 
walula saeliami. This is the greatest of all, and the name means 'hikuli great 
authority.' It is extremely rare among the Tahahumares, and I have not seen 
any specimen of it, but it was described to me as growing in clusters of from 
eight to twelve inches in diameter, resembling waname with many young 
ones around it. . . . All these various species are considered good, as coming 
from Tata Dios, and well disposed toward the people. But there are some 
kinds of hikuli believed to come from the Devil. One of these, with long 
white spines, is called ocoyome. It is very rarely used, and only for evil 
purposes." 

Several of these narcotic hukuli plants are still unidentified. They are 
obviously all cactuses. Several species of Mammilaria have yielded alkaloids 
of undetermined identity, but the genus, which is not far removed from 
Lophophora, might be expected to contain active principles. The same may 



37 



Flowering head of the peyote cactus, Lophophora Williamsii, the "prototype" of the 
New World hallucinogens. Photograph by R. E. Schultes. 

be said of EchinoGactm. In this connexion, it is well known that in Mexico a 
number of species in seven other genera of the Cactaceae — Ariocarjms, Astro- 
phytum^ AzteJcivm, Dolichothele, Ohregonia, Pelecyphora and Solisia — are 
popularly classed as peyote, perhaps because they bear some resemblance to 
the true peyote, Lophophora^ or perhaps because they have similar toxic 
effects and may be employed with Lophophora or as a substitute for it {JfS) . 
There is much, indeed, that needs ethnobotanical clarification in this whole 
picture ; and it Avould seem to be a promising problem (16). All that we know 
is that, of these last seven genera mentioned, three — An'ocarpus, Astrophytum 
and Dolichothele — have yielded alkaloids {65) . 

Witch doctors in northern Peru (in Piura, Lambayeque and La Libertad) 
prepare an hallucinogenic drink called cimora from at least six plants (-?<?)• 
Several of the ingredients are said to be members of the Cactaceae. There is 
indirect evidence of great age for the use of this narcotic drink which is 
concerned with moon rites of the region. It is taken for therapeutic effects, 
for diagnosis and divination, and to make oneself owner of another's iden- 
tity. This intoxicating brew must be potent if the plant ingredients, identified 
apparently without voucher specimens, are correctly indicated. The princi- 
pal ingredient is said to be San Pedro, a cactus, Trichacereits Pachanoi., from 



38 



which the hallucinogenic alkaloid mescaline has been isolated (21). Other 
cactaceous ingredients — a member of the genus Cactus and N eoraimondia 
macrostihas {Oereus macrostibas) — likewise enter the preparation of the 
brew. A further addition is the campanulaceous Isotoma longiflora, known to 
contain the alkaloid lobeline. Pedilanfhm titimnloides of the Euphorbiaceae is 
said also to be added. Datura Stramonium is furthermore cited as one of the 
plants in the formula, and this alone, of course, would provide a potent 
vision-producing base for the drink. With the apparent lack of voucher 
specimens, however, there is no way at present to verify the determination 
of these ingredients. An indication that there may be discrepancies in the 
determinations is that the chief ingredient was at first erroneously deter- 
mined as Opuntica cylindrica {12). It has recently, however, been shown, 
on the basis of botanical collections, to represent Trichocereus Pachanoi., and 
has been ethnobotanically indicated as being a "magic and dangerous" plant 
{18). Whether or not the common name San Pedro applies to both Opuntia 
cylindrica and to Trichocereus Pa/sJianoi., very dissimilar plants, has not been 
verified. 

This problem is further complicated by a recent citation of the "magic 
and dangerous" timora of Huancabamba, Peru, as a species of Iresine of the 
Amaranthaceae {18). Is this timora perhaps the same word as cimora'^. We 
cannot tell at the present time. While several amaranthaceous genera contain 
alkaloids, no such constituents have been reported from Iresine. It is of 
interest to point out, however, that some of the Indians of southern Colombia 
are said to employ Iresine as an admixture in preparing their strongly hallu- 
cinogenic yaje drink {Banisteriopsis spp.) to increase its psychotomimetic 
potency {4^). Here is one of the most challenging problems in the ethno- 
botany of hallucinogenic plants, and one which would not be difficult to 
investigate thoroughly. 

In the late 17th and early 18th Centuries, Jesuit missionaries working 
amongst the Yurimagua Indians in the uppermost Amazon basin found the 
natives drinking a strongly intoxicating beverage prepared from a "tree 
fungus" ". . . the Yurimaguas mix mushrooms that grow on fallen trees with 
a kind of reddish film that is found usually attached to rotting trunks. This 
film is very hot to the taste. No person who drinks this brew fails to fall under 
its effects after three draughts of it, since it is so strong or, more correctly, 
so toxic" {10). Field work in the area has, up to the present time, not yet 
disclosed any practice of this kind, but it is a culture trait little likely to 
disappear spontaneously, at least without leaving traces, and the region is 
still inhabited by tribes in relatively primitive conditions of culture. It has 
been tentatively suggested that the tree fungus might be the known hallucino- 
genic Psilocybe yungensis,^ but what might be the reddish film? Here cer- 
tainly is a most challenging problem in ethnopharmacology. 

The Mojo Indians, an Arawakan tribe living in eastern Bolivia, employ 
an unknown narcotic called marari {34-) . It has been reported that "whenever 
. . . the medicine-men had to interview the spirits, they drank a decoction 
prepared from a plant called marari, similar to our verbena, which caused 

' R. G. Wasson, personal communication. 



39 



Trichocereus Pachanoi growing on the side of a clifiF on the outskirts of Cuenca, Ecuador. 
Photograph by G. Rose. From Britton & Rose: The Cactaceae 2 (1920) fig. 196. 

for 24 hours a general condition of excitement characterized by insomnia 
and pain" {34-) • According to reports, the medicine men try to avoid drinking 
marari whenever they "could operate without the narcotic." This may be 
interpreted as an indication of great potency or toxicity of the drug. By 
likening marari to "our verbena," the French ethnologist Metraux un- 
doubtedly meant Verbena officinalis, a well known folk medicine of Europe. 
The marari might well represent one of the many South American verbena- 
ceous species, but only direct field observation can clear up this enigma. 

Oftentimes, no clear distinction has been made between stimulants and 
narcotics in the writings of early missionaries and other travellers. Guayusa 
is a case in point. Reports of a strongly stimulating plant of the westernmost 
Amazon, widely known as guayusa, place its use in the westernmost Amazon 



40 



of Colombia, Ecuador and Peru. The earliest report of guayusa dates from 
1682 and comprises a missionary reference that pointed to a use surrounded 
by superstition in the region of the upper Maranon in Peru.^ Amongst the 
several references to guayusa, perhaps the most important is that of Richard 
Spruce, who reported it to be a species of Ilex allied to /. paragvuriensis "but 
with much larger leaves" and to be a tonic which, in strong infusions such 
as those prepared by the Jibaros, may be "positively emetic" {59) . 

The recent writings of Karsten (£8) seem to indicate that guayusa may 
have narcotic properties as well, for he states that "just as the Jibaros take 
certain narcotic drinks when they are preparing for war, to see whether they 
will be lucky or not in the undertaking, so they also understand a kind of 
divination in regard to hunting. The drink then used is prepared of the 
guayusa (Ilex sp.), the leaves of which are boiled in water for the purpose. 
The guayusa is not a real narcotic but a tonic, to which the Indians ascribe 
magical purifying effects. The Jibaros, however, seem to believe that the 
drink produces dreams of divinatory significance or, more strictly speaking, 
what they call 'small dreams,' especially such as have reference to hunting." 
Other "supernatural virtues" or magical powers are ascribed to guayusa 
by the Jibaros. 

Even though guayusa may not belong strictly to the category of psycho- 
tomimetic plants, it would be advantageous to know more concerning its 
curious effects — these "little dreams" — that the Jibaros ascribe to the infusion. 
Are these effects wholly imaginary, or may perhaps some other plant be 
occasionally boiled with the guayusa when the "little dreams" are expe- 
rienced ? 

And then, what precisely is guayusa ? Spruce noted that it was an Ilex and 
reported seeing a group of guayusa trees . . . over 300 years old . . . "that were 
not unlike old holly trees in England, except that the shining leaves were 
much larger, thinner and unarmed." A collection of Ilex from eastern Peru 
was described as Ilex Guayusa by Loessener, but it is sterile. Sterile material 
of a guayusa was gathered recently by one of my students in eastern Peru 
and represents undoubtedly an Ilex. It is not wholly improbable that this 
widely disseminated vernacular name may refer to a number of different 
plants with marked physiological action. The guayusa problem is certainly 
one that might occupy the attention of ethnobotanists interested in native 
narcotics and stimulants. It is rather disquieting that even the identity of 
such a plant should, after some three centuries, still be uncertain. 

Another interesting reference concerning a plant with marked physiological 
activity which may or may not be narcotic in character reports the use by 
the Kakusi Indians of British Guiana of "peppers as a stimulant and 
excitant" (4^). Even though the "peppers" were definitely identified as 
belonging to Capsicum, this report should be carefully checked by further 
field observations. 

There is an interesting and very potent narcotic drink used in eastern 
Brazil that merits much more investigation. The Kariri (30) and Pankararu 
{■31 ) Indians along the Sao Francisco River in Pernambuco have an ancient 

' V. PatiSo, personal communication. 



41 



cult, still practiced, connected with a root known as yurema. Groups of war- 
riors or strong young men are given a gourdful of the yurema root infusion 
by an elderly chieftain. With bowed heads, the celebrants see "glorious visions 
of the spirit land, with flowers and birds. They might catch a glimpse of the 
clashing rocks that destroy the souls of the dead journeying to their goal, or 
see the Thunderbird shooting lightning from a huge tuft on his head and 
producing claps of thunder by running about." The yurema rite was formerly 
much more widespread than at present, for it is known to haA^e been practiced 
by at least three other tribes (the Guegue, Acroa and Pimenteira) of the 
general region. The ceremony exists also amongst the Tusha Indians, neigh- 
bours of the Pancararus. 

There is reason to believe that the yurema-drink is the same narcotic as the 
intoxicating beverage of the Pankararus which has been reported under the 
Portuguese name vinho de Jurema. This drink is reportedly prepared from 
the roots of the leguminous tree Mimosa hostilis {W) . Chemically, this plant 
is extremely interesting because of its close relationship to Anadenanthera 
peregrina, from the seeds of which the hallucinogenic yopo snuff of the 
Orinoco River basin is prepared. In 1946, an alkaloid was isolated from the 
bark of the roots o^^Mimosa hostilh^O) and was called nigerine, but recent 
chemical investigation has established the identity of nigerine and N, N-dime- 
thyltryptamine, the same constituent found in yopo seeds fvoTci^nadena,n\ 
(fhera peregrirm j{36) . 

In a remote tributary of the Apaporis River in Amazonian Colombia, the 
Peritome-Tanimukas make use of an as yet unidentified plant to prepare a 
vision-producing drink employed in the adolescent initiation rites of boys 
(57) . It is taken much as is the well known yaje or caapi of the same region 
prepared from Banisteriopsis Caapi^ but the Tanimukas, who employ also 
this malpighiaceous vine, are quick to distinguish the two. The bark of the 
root of an extensive lacticiferous forest liana, without the admixture of any 
other plant material, is subjected to long boiling in order to prepare the 
drink. I was not able to see the vine nor to take the drug during my short 
stay amongst the Tanimukas, but all information pursuant to my question- 
ing was constant. This liana, reported to be rich in latex, might represent an 
apocynaceous species, but the problem cannot be solved until extended field 
work is carried out with these isolated Indians. 

There is evidence that natives of the New World have found psychotropic 
activity in plants introduced from the Old World. It has, for exam- 
ple, recently been reported that Yaqui medicine men from northern 
Mexico employ Genista canari-ensis, the genista of florists, for the purpose of 
inducing hallucinations (17), a property that has been experimentally sub- 
stantiated. The genus Genista and the closely related Cytisus, in which 
Genista canariensis is sometimes included, are extremely rich in alkaloids. 
Cytisine, an alkaloid that formed the basis for the former hallucinogenic use 
amongst some North American Plains Indians of seeds of the leguminous 
Sophora secundiflora {53), has been isolated from leaves and beans of 
Genista canariensis. 



42 



Other Old World plants that may have hallucinogenic uses amongst New 
World natives are several species of the labiate genus Colem. Concurrent 
to the recent discovery by Wasson in the Mazatec Indian country of Oaxaca, 
Mexico, of the utilization of the leaves of Salvia divinorum as a narcotic (63) , 
a similar employment of Coleus putnila and C. Bhimei, both introductions 
from the Old World, was reported. The hallucinogenic effects of the Salvia 
have been experimentally substantiated, and it has been postulated that 
perhaps this plant, native to Mexico, might represent the ancient pipiltzin- 
tsintli of the Aztecs. Chemical examination of Salvia divinorum has not as 
yet disclosed a psychotropic constituent, and analysis of these two species of 




43 



Coleibs, at least on the basis of the reputedly hallucinogenic material growing 
in southern Mexico, has apparently not been carried out. Other species of 
Coleus that are employed in the Old World as folk medicines have, however, 
been studied chemically, but no hallucinogenic substances have been reported 
from them. There is in Turkestan, nevertheless, another reputedly intoxicat- 
ing mint — Lagochilus inebrians (7). The leaves are crushed and mixed with 
honey or sugar for ingestion. A physiologically active crystalline principle, 
lagochiline — a polyhydric alcohol — has been reported from this species {1, 
61)- 

Without any doubt, one of the most fascinating and promising possibilities 
of adding to our list of hallucinogens has recently been brought to my atten- 
tion by one of my former students. Prof. Melvin L. Bristol of the University 
of Hawaii, who spent more than a year in ethnobotanical field work in 
southern Colombia. It concerns the solanaceous genus Brunfelsia in South 
America (57) . A tropical New World genus of about 25 species, Brunfelsia 
plays an important role in aboriginal folk medicine in equatorial America. 
The fluid extract of one species — Brunfelsia Hopeana — is employed pharma- 
ceutically in Brazil as an antidiuretic and antirheumatic. Although atropine- 
type alkaloids — ^brunfelsine, manacine and mandragorine — have been re- 
ported for Brunfelsia Hopeana^ little if anything is known of the chemistry 
of other species {65). The aglycone scopoletine, a coumarine derivative found 
in a number of plant families, has also been isolated from Brunfelsia. Conse- 
quently, we know that this genus does possess active constituents of very 
definite physiological activity. 

Evidence for the narcotic use of Brunfelsia is quite real, but it is not yet 
corroborated by a good body of field observation. Herbarium records are 
very helpful in this instance. There are two collections that indicate the use 
of Brunfelsia as a narcotic. One — Tessmann S2Ii3 from eastern Peru — reports 
simply that the plant is "a narcotic." The other — Bristol 1361i. from the 
Colombia Putumayo — states that the plant is a narcotic and medicinal cul- 
tivated in Kofan Indian houseyards. Other collections of this genus from 
Bolivia, Brazil, Colombia, Eucador and Peru indicate a broad spectrum of 
therapeutic uses ranging from treatment of "yellow fever" to snake bite. Its 
commonest use in folk medicine seems to be to relieve "rheumatism." Several 
collections indicate that Brunfelsia is toxic. In fact, in the vicinity of Leticia, 
a Colombian town on the Amazon River, Brunfelsia maritima {Schultes., 
Raffauf & Soejarto 2Jf.l08) , escaped from cultivation at an abandoned Indian 
site on the upper Amazon in Colombia, has been responsible for serious cattle 
poisoning. The plant is here referred to as sanango^ which seems to be a 
somewhat general term applied in the upper Amazon to several plants with 
medicinal or toxic properties. 

The Kofan Indians of the westernmost part of the Amazon of Colombia 
and Ecuador grow Brunfelsia extensively as an ornamental. They know the 
plant as horrachera. a vernacular term in Spanish applied to almost any 
kind of intoxicating plant, especially to the species of tree-Daturas, in 
Colombia. The Kofan indicate that they become very cold after taking an 
infusion of the scraped bark of Brunfelsia. This characteristic of the in- 



44 




toxication has been reported on herbarium labels of collections from Peru, 
and may well explain the wide use of the plant as a supposed febrifuge. One 
of my graduate students, Mr. Homer V. Pinkley, who has spent a year living 
with the Kof an, reports these medicinal applications of Brunfelsia, but found 
no direct evidence that could be interpreted as indicative of its use as an 
hallucinogen. 

Intensive field work may still uncover a former use of Brunfelsia as an 
hallucinogenic agent in the western Amazon or on the eastern slopes of the 
Andes of Colombia, Eucador or Peru. But Brunfelsia is a genus that needs 
botanical revision and phytochemical investigation. A thorough study could 



45 



Flowering branch of Brvnfelsia maritima, a medicinal and ornamental plant common 
in the western Amazon of Colombia and Ecuador. Rio Aguarico, Ecuador. Photograph 
by H. V. Pinkley. 

reward us with a clearer picture of this possible aboriginal American hallu- 
cinogen. Might its use as an hallucinogen have disappeared? We should 
realise that the disappearance of the use of a plant in a given area is 
not unknown. A century ago, for example, the sapindaceous caffeine- 
stimulant guarana, PauINnia Cupana, was reported by Spruce as cultivated 
all the way up the Eio Xegro of Amazonian Brazil and into southern Vene- 
zuela (59). I found that it has now almost completely vanished from cultiva- 
tion in this region, and the use of the vine as the source of a stimulant is 
imknown along the Eio Negro at the present time. Might not the same fate 
have happened to the solanaceous genus BrunfeUia? 

One of the most interesting enigmas in South America concerns the 
question of whether or not the apocynaceous genus Prestonia is or has ever 
been used narcotically. The literature is rich in reports, most of them un- 
critical and unfounded in field work, that Prestonm amazonica {Haemadic- 
tyon amazonicum) is the source of the hallucinogen known as vaje. All man- 
ner of confusion has attended this information. Although we believe that we 



46 



are warranted in asserting that Prestonia is not employed as a narcotic, there 
remains enough doubt to justify further field investigation {68). What, 
precisely, is the problem ? 

It is well established that a strongly hallucinogenic drink known variously, 
according to geographic area, as ayahvmca., caapi and yaje is prepared from 
one or more species of the malpighiaceous genus Banisteriopsis. Spruce in 



BANISTERIOPSIS Caapi 




47 



1851 first identified the botanical source of this narcotic beverage. He dis- 
covered the natives along the upper Rio Negro in Brazil preparing it from a 
liana which he called Banisteria Caapi. It is now more appropriately ac- 
commodated in a related genus and bears the name Banisteriopsis Gaxipi. 
Several years later, he quite correctly identified a similar drink of the western 
Amazon of Ecuador, where it was cajled ayahuasca. as coming from the same 
species as caapi. 

When he discovered caapi in northwestern Brazil and identified it cor- 
rectly as a malpighiaceous narcotic, he also meticulously observed that an- 
other kind of caapi, known locally as caapi-pinima or "painted caapi," might 
be made from "an apocynaceous twiner of the genus Haemadictyon,'''' but he 
saw "only young shoots without flowers." "The leaves," he wT-ites, "are of 
a shining green, painted with the strong blood-red veins. It is possibly the 
same species . . . distributed by Mr. Bentham under the name Haemadict- 
yon amazonicum. It may be the caapi-pinima which gives the nauseous taste 
to the caapi . . . and it is probably poisonous, but it is not essential to the 
narcotic effect of Banisteria . . ." (59). I have consulted Spruce's unpub- 
lished handwritten field notes at the Royal Botanic Gardens at Kew and 
find his statement that the caapi drink is made from the lower parts of the 
stems of Banisteriopsis Caapi "beaten in a mortar with the addition of water 
and a small quantity of the slender roots of the Apocynac (apparently a 
Haemadictyon) called caapi-pinima . . . ." "May not be the peculiar effects 
of the caapi," he queried, "be owing rather to the roots of the Haemadictyon 
than to the stems of the Banisteria? The Indians, however, consider the latter 
the prime agent, at the same time admitting that the former is an essential 
ingredient." 

Spruce presumed that this apocynaceous admixture might play a role in 
caapi intoxication, but he was not certain. Nor did he make any definite as- 
sertions, pointing out cautiously that the malpighiaceous vine alone produces 
hallucinogenic effects. It was the French anthropologist Reinberg who, in 
1921, without the benefit of voucher botanical specimens, tentatively sug- 
gested the possibility that yaje might be prepared from Prestonia or a re- 
lated genus . Unfortunately, this suggestion has been taken up, its tenta- 
tive nature forgotten or ignored, and is being propagated in technical papers. 

While we know that ayahuasca, caapi and yaje are different local names 
for the same narcotic drink prepared from the same malpighiaceous plants, 
we cannot too lightly dismiss from further ethnobotanical and phytochemical 
study this interesting apocynaceous genus Prestonia^ a tropical American 
group of some 30 species. It is curious that so little is known about the 
chemistry of Prestonia. a member of one of the phytochemically most as- 
siduously studied families of plants {39). No alkaloids have as yet appar- 
ently been isolated from Prestonia. N, N-dimethyl tryptamine has been re- 
ported from '■'■Prestonia amazonica''- {26), but there is every probability 
that this analysis, for which no voucher specimen is available, was made on 
leaves of a species of Banisteriopsis mistakenly identified through the vernac- 
ular name yaje as Prestonia amazonica {58) . The possibility that tliis alleg- 



48 



Makuna Indian witch doctor under the influence of caapi (Banisteriopsis Caapi). Rio 
Popeyaka, Amazonas, Colombia. Photograph by J. Cabo O. 

edly poisonous genus may be the source of an hallucinogenic drug makes the 
solution of the problem one of both academic and practical urgency. 

That there remains much to learn concerning the ayahuasca-capi-yaje 
complex was recently emphasised by the discovery of the narcotic use of a 
new species of a genus allied to Banisteriopsis: Tetrapterys methystica {47). 



49 




It was my good fortune in 1948 to witness the preparation of and take a 
narcotic drink amongst nomadic Makii Indians along the Rio Tikie in the 
Brazilian Amazon. The extremely bitter beverage prepared from this plant 
had strong hallucinogenic effects, was yellowish, unlike the coffee-brown 
Banisteriopsis preparations. It may represent one of the other "kinds" of 
caapi that Spruce reported. 

The identification of various admixtures utilized with Banisteriopsis in 
preparing the nai'cotic drink repi'esents an interesting and still poorly under- 



50 



stood ethnobotanical problem {W). In addition to Prestonia^ which may pos- 
sibly be added to caapi during preparation of the drink, other plants are 
known to be employed in this way in sundry areas, and some of these species 
belong to families and genera that have physiologically active constitutents. 
It is to be supposed, therefore, that they may alter, sometimes significantly, 
the flavour and effects of the narcotic preparation. The Siona of the Colom- 
bian Putumayo, for example, add what is probably Datura suaveolens to 
Banisteriopsis in making yaje (15). The Ingano Indians of the same area 
are said to value Altemanthera Lehmannii as an admixture (-^). I found 
that Makuna medicine men of the Rio Popeyaka in eastern Colombia occa- 
sionally use a few crushed leaves of the apocynaceous Malouetia Tamaquar- 
ina {Jf9). One of my graduate students has recently identified a species of 
Psychotria similarly employed by the Kof an Indians of Amazonian Ecuador. 
A most interesting anthropological report has recently appeared that enu- 
merates five lianas, the barks of which are added to caapi by the Tukano In- 
dians of the Brazilian part of the Rio Vaupes ; unfortunately, these plants 
are as yet identified only by native names {3). How many other plants may 
be used as admixtures throughout the range of use of the South American 
malpighiaceous narcotics ? 

Now, what about the possibility of new hallucinogens in the Old World 
flora? Up to this point, we have concentrated our attention on plants em- 
ployed in primitive cultures of the New World. As I have already men- 
tioned, the New World seems to be far richer in known hallucinogenic plants 
than the Old. The argument that the New World flora might be richer in 
plants possessing psychotomimetic principles would be acceptable probably 
to few chemotaxonomists, including me. There may be several reasons for 
this real discrepancy, but most certainly one might be that Old World cul- 
tures as a whole seem, at least upon superficial examination, to be much 
less narcotic-conscious, to feel much less the "need" for these agents in 
magico-religious rites and in the practice of medicine — and this notwith- 
standing the great antiquity and probably original basic significance of nar- 
cotics to many Old World religious systems. 

There must be an appreciable number of problems in the ethnopharma- 
cological search for new hallucinogens in sundry parts of Africa and Asia, 
but I must content myself with a brief discussion of only a few potentialities. 

What is the famous kanna or channa reported, more than 225 years ago, 
as a vision-inducing narcotic of the Hottentots who chewed it and held it in 
the mouth, much as the natives of South America employ coca ? The intoxi- 
cation is interesting, for "their animal spirits were awakened, their ej^es 
sparkled and their faces manifested laughter and gaiety. Thousands of de- 
lightsome ideas appeared, and a pleasant jollity which enabled them to be 
amused by the simplest jests. By taking the substance to excess, they lost 
consciousness and fell into a delirium" {29). The name kanna designates, at 
the present time, in South Africa, various species of the aizoaceous genus 
Mesembryanthemum. While several species of Mesemhryanthemum are 
known to be alkaloidal and to induce a state of torpor when ingested, at least 
one investigator {29) doubts that they could produce such startling effects. 



51 



The ceremonial clay pot in which caapi is prepared and from which it is served. The 
pot must hang always under the eaves at the left front corner of the house. Barasana 
Indians, Rio Piraparana, Vaupes, Colombia. Photograph by R. E. Schultes. 

He has suggested that the plant in question might have been Cannabis sativa^ 
pointing out, the while, that other plants, like the anacardiaceous Sclerocarya 
Oajfra, are employed in South Africa for their intoxicating effects. Here is 
an area where, because the inroads of civilisation have not been unduly 
drastic, ethnobotanical field investigation might be extremely productive. 

Another Old World genus employed for its narcotic properties is the 
rubiaceous Mitragyna. Mitragyna speciosa seems to be the species most com- 
monly used in southeastern Asia, especially in Siam, where the leaves are 
chewed alone or mixed with the betel quid or else prepared for smoking like 
opium {26). It was first reported as a substitute for opium apparently in 
1836, and has cropped up constantly in the literature since that time {8) . 
The use of Mitragyna is said now to be legally proscribed in Siam. 

So much chemical attention has been given to Mitragyna in recent years 
(5, Jfi) that the problems and potentialities offered by this genus are well 



52 



known. It might, however, be extremely helpful if we knew as much about its 
use amongst the natives. 

Passing mention should further be made of two Old World plants known 
to possess hallucinogenic principles, but the narcotic use of which by native 
peoples for intoxication is not well documented. One of these is Peganum 
Harmala {14),^ rather enigmatic plant that has been placed in the Rutaceae, 
although now it seems more properly located in the Zygophyllaceae. This 
species, native in North Africa, the Balkans and from Asia Minor west to 
China and India, is known to be toxic {6) , to contain the alkaloids harmaline 
and harmine (the same constituents found in Banisteriopsis) , and may have, 
in addition, a "narcotic hasheesh-like alkaloid" {6) . Although the seeds of 
Peganum Harmala have proven narcotic properties and figure extensively in 
folk medicine, going back to the time of Dioscorides, I find no direct refer- 
ences to its religious or hedonistic use as an hallucinogen {37). That it may 
be so employed in Asia or Africa should not be ruled out of our thinking. 

Another similarly interesting narcotic is iboga of the wet tropical forests 
of West Africa, especially of the Congo — the apocynaceous Tahernanthe 
Ihoga {61). Its chemistry is relatively well known, with at least 12 active 
alkaloids reported, the principal one of which — ibogaine — has effects similar 
to that of cocaine {6€) . In high doses, it causes nervous excitement, mental 
confusion, a general state of drunkenness and is a true hallucinogenic agent 
{J^J^) . While it has been valued as a medicine and possibly also as an halluci- 
nogen in primitive societies of West Africa, it is not clear that its use as a 
vision-inducing narcotic was extensive. Ethnobotanical field work is once 
again indicated. 

There have been vague references to the zingiberaceous Kaemfferia 
Galanga., to which the natives of several parts of New Guinea attribute hal- 
lucinogenic properties (^). We know, in fact, nothing about the psycho- 
tomimetic use of this genus, nor of its chemical constituents. 

The role of mushrooms in the so-called "mushroom madness" of the Kuma 
people of the Wagti Valley in New Guinea has been, and still is, puzzling. A 
species of Russula has been suggested as the psychotropic agent that suddenly 
causes individuals or groups to go berserk. Even though the "natives attrib- 
uted their extraordinary behaviors to mushrooms, several species of Boletus., 
Russula and Heimiella — or at least most of them — do not seem to cause 
physiological effects leading to madness." {2^) . I am convinced that much 
more field work must be done in this fascinating part of the world. 

Undoubtedly the greatest enigma in the field of the hallucinogens has 
been the identity of soma {61). Some 3,500 years ago, a people Avho called 
themselves Aryans, who were the first so to style themselves and who had 
a right to the name, swept down from the north into the Indus Valley of 
India. They brought with them the cult of a sacred plant, called soma. They 
deified the plant and Avorshipped it, extracting its juice and drinking it. 
They composed more than one thousand hymns about it, and these have come 
down to us intact. 



53 



What was soma? No one knows at the present time. For more than two 
thousand years, its identity has been clouded in a mystery. For some un- 
explained reason, the Aryans abandoned the original plant soon after they 
arrived in their new home, and its identity was forgotten. Other plants took 
its place as substitutes — plants chosen for reasons other than the psychic 
effects which, in the case of the substitutes, seem to have been non-existent. 

Western civilization discovered the enigma of soma about a century and 
a half ago when it began to learn about the cultural wealth that India had 
to offer to the world. Since then, more than a hundred species have been 
suggested as the source of the original soma, but none of the suggestions 
has won acceptance. Amongst these, the principal contenders were numerous 
species of Ephedra, Periploca and Sarcostemma: the first genus a gymno- 
sperm ; the last two asclepiadaceous genera ; but all similar in being vine-like, 
fleshy, leafless or almost leafless desert plants. 

For some years now, Wasson has devoted full time to a deep study of the 
historical, literary and ethnobotanical records concerning soma. He has spent 
several years in the Far East and much time in European university centers 
and libraries. We are justified in stating, I believe, that never has greater 
thoroughness and meticulous scholarship gone into the enigma of soma, for 
Wasson's avenues of ethnobotanical research have been ingeniously devious 
and complex. "When I first approached the problem in 1963," he {63) wrote, 
"I could hardly believe what I found ... a clear-cut botanical question — a 
psychotropic plant that calls for identification. The clews should be in the 
Vedic hymns . . . True, the poems contain no botanical description . . . for 
those remote singers were not modern botanists . . . they were writing for 
contemporaries . . . and their imagery and terms often elude our under- 
standing . . . But the hymns are all shot through with soma, and about 120 
of them are entirely devoted to the plant-god. Was it possible that so much 
could have been written about a plant, over centuries . . . and its identity not 
revealed ? It was no secret for the poet-priests. How extraordinary it would 
have been if all of them . . . had withheld from their verses the revealing 
descriptive terms, the tell-tale metaphors, that the trained reader today 
needs to spot the plant ! But this did not happen. All that has happened is 
that no ethnobotanist with an interest in psychotropic plants has applied 
himself to an examination of the texts." 

To this age-old enigma, Wasson has suggested a solution: that the true 
soma was a mushroom, the fly agaric, Amanita rrvuscaria, the same mushroom 
used narcotically today by certain natives in Siberia. All of the many intri- 
cately interlocking pieces of indirect evidence gleaned from the Vedic hymns 
seems to fit in with this clever suggestion so well that Wasson has asked : 
"Could any key unlock this combination save the fly agaric?" He is now 
engaged in writing his conclusions and, in view of his contributions to our 
knowledge of the sacred Mexican mushrooms, of the narcotic morning- 
glories and of the new hallucinogenic Salvia, of Mexico, we await the comple- 
tion of his fascinating study with great anticipation. 



54 



Guidelines for the Future 



The ethnobotanist, especially in his ethnopharmacologic search for hal- 
lucinogenic plants, is confronted with these and many more problems through- 
out the world. Faced with the ever more rapid disintegration of primitive 
societies and an extraordinary dearth of trained ethnobotanists, science 
would seem to be doomed to lose. The outlook, however, may not be so dour. 
Specialists in those fields upon which ethnobotany impinges are experiencing 
a growing realization of the potentialities of the interdisciplinary approach 
that ethnobotany affords. There is growing interest in ethnobotanical 
research amongst younger men going into botanical, anthropological and 
pharmacological fields. Some of the most startling scientific advances of the 
past twenty years have been made in various branches of ethnobotany. The 
future should, therefore, solidly be ours, and our trust must be to prevent 
its slipping from us. 

It might here be appropriate to end with the words of Harshberger, author 
of the term ethnobotany^ who wrote: "It is of importance ... to seek out 
these primitive races and ascertain the plants which they have found avail- 
able in their economic life, in order that perchance the valuable properties 
they have utilized in their wild life may fill some vacant niche in our own." 

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262-016 0-67— 6 



57 



Empiricism and Magic in Aztec 
Pharmacology 

Efren C. del Pozo 

Instituto de E studios Medicos y Biologicos 
National University of Mexico 

Indigenous pharmacology is always based on empiricism ; however, magic 
procedures and religious ceremonies are often mixed in medical use. When 
a plant has been found to produce marked physiological effects it is likely 
than an explanation for those properties is to be looked for according to the 
substratum culture of the particular ethnic group. 

That has been the case for coca, "the divine plant of the Incas" ; for peyotl, 
"divine messenger"; teonanacatl, "God's flesh." These examples show that 
the magic or religious associations could not be taken as evidence of lack of 
empirical knowledge. Many times a plant used by medicine-men or priests 
has been found to be an active pharmaco. 

However, the astronomical number of plants, minerals and animals used 
in popular medicine prescribed by all sorts of medicine men, herb-vendors, 
magicians, shamen, or used directly by the people, prevents an indiscriminate 
study of all this materia medica. 

An ethnoiatric study (i) from the standpoints of social, historical, reli- 
gious and philosophical contexts, is required for the evaluation of the medical 
uses of a community. Moreover, even for pharmacology, an extensive knowl- 
edge of the socio-cultural background and environment of a tribe is needed 
for understanding the orientation and purposes in the use of a drug. 

The case of Azetc pharmacology is a very peculiar one. A brief history 
of Aztec civilization will help to evaluate the problem : 

The Aztecs were a nomadic and primitive group that arrived in the Mexi- 
can Valley only two hundred years before the Spanish Conquest. They had 
been conducted and governed by a witch called M alinalxochitl, and later on 
by a warrior, Huitzilopochtli. They encountered in the Valley of Mexico 
human groups, the Nahuas, of much higher cultural development and with a 
religion based on spiritual values inspired by the great Quetzalcoatl, a god or 
perhaps a man full of wisdom, who gave to the Toltecs codes of ethics and 
love for art and science. All the Nahua groups settled in the Valley of Mexico, 
inheritors of the old Toltec civilization already disappeared, had a great 
veneration for Quetzalcoatl, god and man, father of knowledge and morals. 
Human sacrifices, the horror of Aztec Society, were not practiced among the 
N ahuas before the Aztec arrival {2) . 

The incongruity of a well-advanced culture with high moral principles as 
taught by the Calmecac or Aztec College, and brutal ritual butcheries, are 
to be explained by the merger of two different thoughts. One, the Toltec, 
spiritual and learned; the other, the original Aztec, magical, bellicose and 



59 



One of the multiple representations of Quetzalcoatl (Codex Borbonicus). 

imperialistic. The Aztecs brought under their command all the Nahuatl 
groups through wars, treachery and terror, but took advantage of all the 
knowledge and cultural development of the conquered nations. They adopted 
the Quetzalcoatl title for their highest priest, paid devotion to Quetzalcoatl 
teachings and myths, and kept great respect for Toltec traditions {3) . 

Sahagun, the most eminent Spanish priest who studied the Mexican culture 
in the XVI Century, said with regard to the Toltecs : "They had great ex- 
perience and knowledge : They knew the quality and virtues of the herbs, and 
they left marked and known those that nowadays are used for healing, be- 
cause they were also physicians and essentially the first in this art. . . . They 
were the first inventors of medicine ... So able were they in natural 
astrology . . . that they were the first to count the number of days in a 
year . . . They invented the art of interpretation of dreams, and were so 
learned and wise that they knew the stars of the sky, had named them and 
knew their influences and qualities. They also knew the movements of the 
skies through knowledge of the stars . . . The said Toltecs were good men 
and lovers of virtue ..." (4). 



60 



When in 1519 the Spanish Conquerors arrived in Mexico they found a large 
number of nations or tribes under the tyrannical rule of Tenochtitlan 
Emperor. They were forced to pay heavy and growing tributes, and very 
often to provide human beings for the continuous sacrificial ceremonies at 
the Aztec capital. These sacrifices sometimes reached the incredible number 
of several tens of thousands of human beings, according to several Spanish 
chroniclers. No wonder that Cortes and their men easily found allies among 
those subjugated people, who candidly thought they would obtain their 
freedom. 

The fall of the Aztec empire to a handful of Spanish adventurers was 
also helped by the magic-minded Moctezuma, who had a series of dreams and 
other warnings about the imminent return of Quetzalcoatl. 

The complexity of Mexican culture was greatly increased by the arrival 
of the Spaniards who brought about movements of tribes, displacement of 
towns, mixtures of people, and emigrations. Terrible wars, destructions of 
cultural centers, persecution of all people representative of old beliefs and 
religious and magical practices, were systematically carried out in order to 
annihilate the influence of the devils. The new religion and the European 
concept of the world were enforced. 




Xochipilli {Magliabechi 23) 



Representation of Xochipilli, god of flowers, joy and love (Codex Magliabechi) . 

61 




Hommage to Cortes, the Spanish Conqueror, at the time of his arrival. (Lienzo 

Tlaxcala) . 

Aztec medicine, as every other field of that culture, was shaken by the 
arrival of the European conquerors. The most distinguished people who 
ordinarily set the standards and regulations for the practice of any profes- 
sion, were killed or removed. The Aztec priests, the most learned people 
trained at the Galmacac^ were also killed or prosecuted, and the officers and 
distinguished representatives of every civilian activity were deposed. All 
people practicing medicine or any art of healing had to work at their maxi- 
mal capacity trying to help the thousands and thousands of wounded, in- 
jured and sick all over the destroyed towns. Devastating epidemics followed 
the fall of the Aztec civilization. All books containing their knowledge and 
tradition in every field were systematically burnt. 

Fortunately, the most learned Spanish priests who came to evangelize, had 
a great need of knowledge of the indigenous "superstitions" to enable them- 
selves to prosecute evil and indoctrinate in the new faith. They went deep 
into a thorough study of indigenous rites, gods, religions, history, knowledge 
and morals of the newly conquered people. They learned the native languages 
and wrote dictionaries and grammars to assist the ordinary priests in their 
catechization work. 

Some of them became seriously interested in the real value of mexican 
civilization, and developed extensive studies to obtain data and information 



62 



about every aspect of those cultures. The most distinguished of them, Fray 
Bernardino de Sahagun, was a true pioneer in the use of scientific methods 
for ethnological research. He obtained reports from groups of well-selected 
informers, specialists in every field, and kept protocols in Nahuatl of their 
statements. He wrote his well-known "General History of Things of New 
Spain" (4) based on that data. However, only recently have his protocols 
received attention, and are being translated from Nahuatl into Spanish 
(5) and English (6) . 

Another important fact to be mentioned in order to evaluate the informa- 
tion tlM has reached us is the establishment in 1536 of the Colegio of Santa 
Cruz de Tlatelolco, which was founded with the purpose of indoctrination 
in European culture of the potentially dangerous youngsters descending 
from the previously ruling class. These students became very valuable as- 
sistants to Father Sahagun and other priests, and even reached positions 
as lecturers in their own College. We certainly know that one of them, Juan 
Badiano, was a teacher of Latin and translated the only book of medicine 
we have that was written directly by an Aztec physician, Martin de la Cruz. 

It is evident that Aztec pharmacology at the beginning of the XVI 
Century had reached an important degree of development: The multiple 
and well-kept botanical gardens mainly devoted to growing medicinal plants 
were known and admired not only by Cortes and his soldiers, but by botanists 
and physicians. Francisco Hernandez, physician to Philip II, collected, 
described and assayed, numerous plants from those gardens, particularly 
from the one at Oaxtepec (7). 

The discovery of the medicinal properties of those plants was undoubtedly 
empirical. Contemporaneous chroniclers report that at those botanical 
gardens the plants were given free to the patients, under the condition that 
they would inform about the results. In addition to this example of in- 
stitutional research, we have evidence that the professions of physician and 




The conquerors receive assistance from local Indians for the transportation of all sort 
of materials, At right lower angle is shown an example of the means used to obtain 
cooperation (Lienzo de Tlaxcala). 



63 



herb-vendor were practiced by individuals other than those devoted to sor- 
cery, magic, witchcraft and religion. We are aware that active plants, mainly 
those with hallucinatory properties, were used by sorcerers and priests 
together with their own paraphernalia. 

It is a difficult matter to say what part is played by the pharmacodynamic 
action of a drug, and what is due to suggestion, when psychological proce- 
dures are added. The test of healing has always been poor evidence of 
efficacy. However, in a long run, a conclusion based on repeated experience 
may be reached. 

The plants used in Aztec medicine are mentioned in several chronicles, but 
ordinarily only the names are given and these in the Nahuatl language. In 
the case of the Cruz-Badiano manuscript, wonderful color illustrations were 
added in order to help the European people identify the plants, but even 
with this data, botanical identification has been difficult. After four and a 
half Centuries many of the plants contained in the materia medica of the 
Aztecs remain unknown. 

Some authors (8) have thought that Sahagun and other chroniclers gave 
a too rationalistic idea of Aztec medicine because they tried with the 
European rationalistic mind to adjust what they saw to what they knew. 
However, remember that we have the almost verbatim protocols recorded 
in Nahuatl by Sahagun and his mexican assistants, which in this matter coin- 
cide with his writings. We believe that these protocols contain an almost 
literal transcription of the answers given by the informants because, written 
in Nahuatl, they maintain the peculiar repetitive structure of that language. 
Series of adjectives, verbs or phrases, one after another, make clear or em- 
phasize the concepts. That style appears in the protocols but not in Sahagun 
History. 

In order to have examples of XVI century European "rationality'" in this 
matter, a few quotations may be useful : 

"Thieves knew very well of enchantement, with which they used to deaden 
or made to faint the dwellers of a house, and then stole everything to be found, 
and even with his enchantments took out the barn and carried it on his 
back ..." (Sahagun) {4). 

The enchantments and carrying of barns do not appear in the informants 
texts, which means that this data is the responsibility of the writer. 

"I was called to confess an indian woman . . . because she was dying from 
a flux of blood by mouth. ... I had a piece of bone of the Saint and Vener- 
able Gregorio Lopez ... in a spoon of water I gave her to drink a little 
of the bone . . . and as soon as she drank it, she felt relief. . . ." (de la Ser- 
na) {9). 

"There are also some stones called eztetl which means stone of blood . . . 
I had experience of the virtue of this stone because I have one as big as a fist 
or a little less ... in this year of 1576 during this pestilence it has given life 
to many whose blood and life were going out from his nose. Taking it (the 
stone) in their hand and liaving it for some time the bleeding stopped and 
they recovered from this disease from which many have died and are dying in 



64 



all this New Spain. There are many witnesses in this town of Tlatilulco of St. 
James" (Sahagun) {4)- 

Undoubtedly in order to judge the Aztec medicine in its entirety it is re- 
quired to try to understand the cultural and religious atmosphere of that 
people living under exceptional conditions of anguish. Their own blood was 
required to keep the sun shining, everything was under the influence of exact- 
ing gods and thousands of major and minor priests were interpreters of the 
holy designs. Diseases, particularly when chronic, grave or epidemic, were 
considered as divine punishments for the group or the individual because of 
deviations from the strict rules of behaviour. 

But religious, magical and other psychological methods were also used in 
order to solve ailments that had not responded to ordinary treatments. Un- 
der the circumstances described by Sahagun, one is inclined to believe in the 
effectiveness of his large stone estetl, to stop epistaxis when that exceptional 
mineral was held into the tightly closed hand of the patient. The emotional 
liberation of epinephrine could explain that effect. 

Sorcerers and priests used to give to patients and drink themselves ololiuh- 
qui and mushrooms to produce hallucinations which would give them leads 
about the origin of a disease and the way to cure it. 

All these facts could give the impression of an impenetrable mixture of 
magic, religion and empiricism in Aztec therapeutics, but that would be the 
case if we put together all the resources that present day people many times 
put in action when they suffer a grave or incurable disease. 

Sometimes it is very difficult to decide if a practice is rational or magic, be- 
cause there is interaction of procedures and influences. The use of amulets, 
stones, relics, conjures, is not magic any more when they are heavily charged 
of psychological meaning or had established conditioned reflexes. 

Even the classical magician technics based on the use of music (melo- 
therapy), odors (osmotherapy), colors (chromotherapy), dances, cabalistic 
words and phrases (versotherapy), are not to be disregarded as baseless. 
Those methods represent sensorial stimulations that could provoke favourable 
neuro-endocrine reactions. 

If we fix our attention to pharmacology the problem has to be envisioned in 
a different way. It does not matter if a pharmaco has been used by a physician, 
a sorcerer, a witch or a medicine-man, if we have some evidence of a definite 
effect. 

We know that Aztec pharmacology was based mainly in the use of plants 
selected by a long empirical testing. Present day laboratory assay has con- 
firmed the activity of many of them. We are now interested in psycoactive 
drugs. The Aztecs gave us teonanacatl, peyotl, ololiuhqui, piecetl, toloatzin, 
already attested in their activity. There are others that have to be studied. We 
need no proofs that the action of those plants was discovered by empiricism. 
We would be magic minded if we would suggest that they had reached the 
hands of the sorcerers by supranatural inspiration. We have no reason for 
any doubt on what the XVI Century chroniclers tell us about the well trained 
Aztec physicians with an extensive knowledge of medicinal plants and long 
experience in diagnosis and treatments. Sahagun said very clearly that they 



65 



would not use sorcery and gives names of every one of the members of the 
group that he selected as informants for the chapters on medicine and related 
subjects of his History : "This relation given above of the medicinal herbs 
and the other medicinal things above contained was given by the physicians 
of Tlatilulco, James, old and very experienced in those things of Medicine ; 
all of them are in general practice. The names of them and of the amanuensis 
that wrote it are the following, who, because they did not know how to write, 
begged the amanuensis to put their names: Gaspar Matias, neighbour of 
Concepcion, Pedro de Santiago, neighbour of Santa Ines, Francisco Simon 
and Miguel Damian, neighbours of Saint Toribio, Felipe Hernandez neigh- 
bour of Santa Ana; Pedro de Requena, neighbour of Concepcion, Miguel 
Garcia, neighbour of Saint Toribio, and Miguel Motolina, neighbour of 
Santa Ines". 

It is surprising that Martin de la Cruz was not among them. He was 
the physician at Santa Cruz de Tlatelolco, Sahagun's beloved College; he 
wrote the book on the medicinal herbs of the Indians that was translated into 
latin by Juan Badiano. He could have been absent or dead, but we can 
not explain the fact that Sahagun does not mention the exceptional and 
wonderful book written on a subject he was studying at that time and 
when he refers in extenso to that School. 

In a study of mine included in our recent edition of the Martin de la 
Cruz and Juan Badiano book, I discussed this strange fact and arrived 
at the conclusion that Sahagun might have considered Martin de la Cruz 
already under the influence of European medicine. In fact, many signs 
could be found of that contamination, mainly the names of diseases, the 
pharmaceutical mixtures and even the presence of a reference to Pliny {10). 

It is a pity that the only book on medicinal plants written by an Aztec 
physician has to be read with a critical eye, because of European influences. 
It is interesting to note that ololiuhqui, peyotl and teonanacatl do not 
appear in the book, either because the use of them was exclusive for sorcerers 
or because of church censorship. On the other hand, many prescriptions 
that seem magical because they contain strange substances, now known 
inert, only means pharmacological mistakes. Lack of activity does not 
show absence of rationality in the use. Magic implies the performance of 
acts, pronunciation of words in presence of particular objects, from which 
only the magician or wizard is capable of managing to produce the effect {1). 
Nothing of that sort appears in the book : medicines could be used by anybody 
without devices or spells for supernatural powers {11)- 

Magical practices in Aztec society had their own fields and practi- 
tioners: sorcerers, necromancers, witches and magicians. However, there 
are no records of true shamans as defined by Mircea Eliade (-?^), that is 
with techniques for ecstasy and initiation ceremonies as practiced in Siberia. 

Sahagun had left us the description of several of those professions : "The 
naonlli is properly called sorcerer; he frightens men and sucks blood from 
children during the night" (.^). "The necromantic [tlacateculutl) has a 
pact with devil ; he transforms himself into different animals, and because 



66 



MARTIN DE LA CRUZ 



LIBELLUS DE MEDICINALIBUS 
INDORUM HERBIS 

MANUSCRITO AZTBCA DB 1552 

Segiin traduccidn latim de 
JUAN BADIANO 

VERSION ESPANOLA CON ESTUDIOS 
Y COMENTARIOS POR DIVERSOS AUTORES 



INSTITUTO MEXICANO DEL SEGURO SOCIAL 

MEXICO 
1964 

Title page of the recent edition of Martin de la Cruz' book (Institute Mexicano del 

Seguro Social, Mexico, 1964). 



of hatred wishes death for others, using sorcery and many charms against 
them." {J^) . 

The same Sahagun refers to the ticitl or physicain in a very different 
way: "The physician (ticitl) used to cure diseases and restore health; the 
good physician is a knower of herbs, stones, trees and roots, experienced in 



67 




Folio 3S V. of Martin de la Cruz manuscript. Notice the Aztec representation of stone 

''tetV in the roots of five of these plants. 

cures. He also has the profession of knowing liow to set bones of people, 
to purge thern. bleed them, to make incisions in them, to sew the wounds 
and to free people from the doors of death. The bad physician because he 
is not able, ha place of curing the patients, worsens them with his potions. 
At times he uses sorceries and superstitions to make believe that he makes 
good cures"" (4) . 

All precoltmibian codices were intentionally destroyed, but we should 
remember that because of the lack of a true written language those documents 
were only guides for learned people, usually trained at the Cahnecac who 
memorized the traditions, history and knowledge of that people. The destruc- 



68 



tion of that material, temples, sculptures, and every testimony of that cul- 
ture, was thoroughly carried out for many years with all the zeal of the 
most fanatical epoch in the history of Spain. The Holy Inquisition soon was 
prosecuting any man denounced because of keeping in his house objects 
corresponding to superstition, witchcraft, rites, gods, idolatries and other 
uses of gentilism (13). 

After the Conquest everything related to Aztec culture went underground 
and declined. When the leading representatives of pre-hispanic medicine 
were dead or had disappeared, it is natural to suppose that the standards of 
general practice would deteriorate. XVII Century descriptions of medical 
practices do not correspond to what had been said a Century before. 

This shows the fundamental mistake of people who pretend to draw 
conclusions about Aztec pharmacology by studying the practices of present 
day Indian communities. Today, Nahuatl groups live in extreme poverty in 
"refuge localities" far away from civilization; they live in ignorance and 
poor health. These degenerated vestiges of the Aztecs retain no inheritance 
from their glorious ancestors. Four centuries of isolation and neglect have 
left the people without most of the values of their culture ; even their physical 
condition has been affected. 

Nobody could expect to obtain from them astronomical or mathematical 
data, nor to find the marvelous sculptors and architects that left us impressive 
evidence of their inspiration. However there are investigators who pretend to 
judge Aztec medicine or pharmacology from the present practices in these 
deteriorated groups. 

Ethnopharmacologic research in Mexico has a great work ahead for 
exploration of the Nahuatl knowledge and experience with plants. Many 
writings have not been studied thoroughly. There are documents that have 
not been translated or interpreted. A great number of plants described under 
Nahuatl names have not been botanically identified. Some of them, painted 
with colors in the Cruz-Badiano manuscript, have escaped classification. 

Botanical Imowledge was advanced among the Aztecs. They had made 
groups of plants according to morphology, size, structure, fruits and their 
uses m)- Medicinal plants was one of those groups, but the system allowed 
having many different plants with the same name. Hernandez used to add 
to the Nahuatl name of the plant the name of the nearest town where that 
specimen had been collected (7) . The color paintings obtained by Hernandez 
would have helped for identification, but they were lost in the fire of the 
Escorial library in 1671. The drawings published in black in the Lincei edition 
of the New Spain Thesaurus (15) were redrawn from the originals (16). 
These figures were used again for our recent first complete edition of Hernan- 
dez Natural History (7) . 

A great many of the plants described by Hernandez have not been identified, 
and now collecting expeditions are planned in order to follow Hernandez' 
routes in Mexico. It is expected that fresh specimens will allow identification 
of some of the species described by the Spanish physician in the XVI 
Century. 



69 



FRANCISCO HERNAnDEZ 



Protomedico e HistorinJor del Key de Espaiiii, 
Don Felipe II, en Im bidias Occidentales, 
Islas y Tierra Firme del Mar Oceano 



OBRAS COMPLETAS 
TOMO II 

* 

HISTORIA NATURAL DE NUEVA ESPANA 
VOLUMEN I 




UNIVERSIDAD NACIONAL DE MEXICO 
1959 

Title page of Volume 1 of the recent edition of Hernandez "Natural History of New Spain" 
(Universidad Nacional de Mexico, Mexico 1959) . 



70 



Looking for an orientation to pick out active plants used in Aztec medicine 
we compared different reliable reports. We thought correlation would indicate 
reputation or general use of the plant. However the results did not justify our 
premises : 

Sahagun mentions in his History 123 medicinal plants and only 86 of them 
appear in the texts of his informants. This means that he made a rigorous 
selection and that he used other sources of information that we do not know. 
The comparison of his protocols kept in Madrid and Florence libraries, 
showed only 78 plants in common. Of a total of 225 different plants in those 
texts, 163 appear in the first and 140 in the second. This is new proof of the 
differences between both manuscripts {10) . 

When we compared the botanical content of the materia medica in the 
Cruz-Badiano book, we discovered the surprising fact that among 251 plants 
mentioned there are only 15 of those included by Sahagun in his History. 
However, 14 more appear in the Informants' texts. We could speculate about 
the already mentioned possibility of basic discrepancies between the pro- 
fessional training and methods of Martin de la Cruz, physician at the Span- 
ish College of Tlatelolco, and the Indian physicians put together by Sahagun, 
who were general practitioners among his folk. 

Furthermore the plants that are mentioned in both documents sometimes 
appear with different therapeutic indications or they are not granted similar 
interest : tlatlancuaye (plants of the genus iresine) appear 17 times in Martin 
de la Cruz, only once in the texts of Sahagun informants, and none in his 
History. 

With regard to Francisco Hernandez Natural History, we should remem- 
ber that he was an European physician, representative of the medical and 
philosophical ideas of "humors" and qualities of diseases, and for the "con- 
traries" or medicines. In that way Hernandez described 3076 plants and 
gives the "dryness" or "humidity", "warmness" or "coldness" degrees of every 
one of them. According to those European doctrines any plant could be useful 
in medicine if its qualities were contrary to the nature of disease. Once he says 
how bewildered he was at the use by the Indians of warm plants against fever. 

We know that Hernandez was sent to New Spain to study the medicinal 
plants in the newly conquered land but he, as a naturalist, devoted himself to 
a wider field. During seven years, disregarding the royal and urgent requests, 
he kept collecting and assaying plants and writing his Natural History, 
instead of obeying the orders for sending his manuscripts. The large extension 
of his final report and his wider scope perhaps were the origin for the king's 
decision to entrust somebody else to make an abstract of his writings. That 
commission given to Recchi was greatly resented by Hernandez. 

The difference between the approaches of the writings I have mentioned 
are evident : Martin de la Cruz wrote about the plants used by him and his 
kindred Indian physicians; Sahagun strived to obtain uncontaminated in- 
formation about the pre-hispanic uses of plants by the best known physicians, 
uses that he described independently of the practices by sorcerers, wizards and 
soothsayers ; Hernandez worked as a naturalist collecting specimens by him- 
self and obtaining information on the spot about the popular uses of the 



71 



TRrS GRABAROS DK HISTORIA NATIIRAK, MAXIMI PIRICRINAI 445 




TENOCHTLI 

(Libro VI, cap. cx) 



Nieremberg figures taken from Hernandez' originals that were kept at the Escorial 
library. Note the Aztec hieroglyphs for water (atl) under Atatapalcatl and for stone 
(tetl) under tenochtli. 

plants. No wonder the reports differ. But they complement themselves if one 
analyzes the meaning of the data by keeping in mind the wide distance 
between the standpoints of view. 

We have talked about only three of the most reliable sources, but there are 
many other important chronicles and writings, contemporaneous and pos- 
terior. Sometimes late reports relative to cultural and living conditions of 



72 



TRATADO 

DE LAS 



mmmm i mmim mnm 

QUE OY VIUEN 

ENTRE LOS INDIOS NATURALES 

DESTA NUEUA ESPANA. 

ESCRITO EN MEXICO 

FOR EL BR. HERNANDO RlIZ DE ALARPON. 

A^O 1629. 



PRIMERA EDICION. 



MfiXICO. 
1892 

Title page of the 1892 edition of Ruiz de Alarcon book written in 1629. 



262-016 0-67— 7 



MANUAL 



MINISTROS DE INDIOS 



VAWA III COXOi'lHIKNrn 



DE SI'S IDOLATRIAS. Y EXTIRPATION UE ELLAS. 



DEDICAIXI 



AL 1IJ.H0. HK. OH. ». HATHEO DE ZA»A DE HUtiVEIRO, 



COLEUIAL DKL DK FOKHELA SN SAKflACO PI GaLICU, 

V dilMavob db Santa Csi'z de Valladoud. tu Rectoe, Cathedeatico de lkteae huiiahaii ex la Vmivbcridad ue CoiirosTFi.A, 

E^( I.A DE VaLLADOLID I>B I.AS CaTHEOEAS de PhILOHOPHIA DK DUEAHDO V DE PBINA DE SaCBADA EaCBITVBA. 
CaMONIGO DB LA SaKTA IglHSIA ue AtTOBCA. 

Machtbal de la Imfsbial he Toledo, 

ABtOHIHPit Vf- LA SaXTA tr.LEfltA UkTBOPOLITANA I>1- MkxUO, UKl. CON&RJO DF S. U. 



COMPIESTO 



POR EL DR. JACINTO DE LA SERN A, 



NATt'BAL DE MEXICO, 

Rector dos veces del Colegio V'iejo ue Todos Santos, 
Db. Theologo de esta Imperial V'niversiuad, Rector ires veces de ella, 

Cl'RA MAS ANTIGl'O DEL Sa(;RARIO DE ESTA SaNTA IgLESIA, 

\'isiTADOH General 

DE LOS Se.^'ORES ArZOBISI'OS D. KhAXCISCO Ma.VSO, Y L). Jl AN DE MaSOSCA, V EXAUINADOK SiXODAL 

OF I.OS MISMOS GOVIERNOS. 



PRIMERA EDICION. 



MfiXICO. 

IMPRKNTA. URI. MTJSKO NACH)KA.I.. 

1892 



Title page of the la Serna book. 



the Indian population at the time of the observation, try to refer to the pre- 
hispanic society. That error is evident in XVII and XVIII Centuries writings 
when the old ruling class had disappeared and the Indians, deprived of their 
land, had been distributed as slave workers to the new owners. New religion 
and magic, new medicine and superstitions had been imported, and African 
rites and witchcraft had arrived with the African slaves brought by the 
Spaniards. 

Ruiz de Alarcon, who in 1629 wrote one of the best known treatises on 
native idolatries {13) recognizes those facts and mentions that the Indians 
were dying at a fast rate because of bad health and drunkenness a vice not 
allowed in Aztec society. 

Present research requires most careful analysis of data. No doubt we could 
still find valuable information, but great patience and comprehension have 
to be used in order to overcome the natural distrust of people that have been 
subjected to exploitation during Centuries. 

Documents on magic are difficult to study. Translations and interpreta- 
tions are full of problems because of the esoteric language {Nahuatlatolli) . 
Literal translations refer to "the nine times beaten" for tobacco, the "red 
chichimec" for copper, the "red woman" for blood, "one water" for wood, 
"seven caves" for mouth, "snake" for pain (,9) . Most of these imaginative ex- 
pressions have not been explained and many others have not been interpreted. 
As we say before, magic and its language represent very old myths and such 
study is full of obstacles. 

The scientific study of Aztec pharmacology is very recent and has already 
given important discoveries. Many more will come if capable people from 
different fields work together. The personal work of Gordon Wasson and 
the valuable contributions from people inspired by him, is a good example of 
what has to be done {17). This symposium on an even wider scope, inter- 
nationally oriented, is a promising step for closer collaboration. 

REFERENCES 

(i) Scarpa, A., "Nozioni di Etnoiatrica," Stamperia Valdonega, Verona, 1962. 
{2) Sejouene£, L., "Buming Water. Thought and Religion in Ancient Mexico," 
Thames and Hudson, London, 1956. 

(3) Caso, a., "El Pueblo del Sol," Fondo de Cultura Economica, Mexico, 1962. 

(4) SAHAGtJN, B. DE, "Historia General de las Cosas de Nueva Espana," Fornia, Mexico, 

1956. 

(5) Garibay, a. M. and Le6n Portilla, M., "Fuentes Indlgenas de la Cultura Nahuatl. 

Informantes de SahagHn," Universidad Nacional de Mexico, I, 1958 ; II, 1958 ; III, 
1961. 

(6) Anderson, A. J. O. and Dibble, C. E., "Florentine Codex." School of American 

Research and University of Utah, Sante Fe, New Mexico, II, 1950 ; III, 1951 ; 
IV, 1952 ; V-VI, 1957 ; VIII, 1953 ; IX, 1954 ; X, 1959 ; XI, 1961 ; XII, 1963 ; XIII, 
1955. 

(7) Hernandez, F., "Historia Natural de Nueva Espana," Obras Completas. Univer- 

sidad Nacional de Mfeico, 1959. 
{8) Aguirre Beltban, G., "Medicina y Magia." Instituto Nacional Indigenista, Mexico, - 
1963. 



75 



(9) DE LA Sekna, J., "Manual de Ministros de Indios, escrito en 1656." Imprenta del 
Museo Nacional, Mexico, 1892. 

(10) DEL Pozo, E. C, "Valor mMico y documental del manuscrito." In de la Cruz, M., 

Libellus de Medicinalibus Indorum Herbis, Ms., 1552, Instituto Mexlcano del 
Seguro Social, Mexico, 1964. 

(11) DE LA CKrz, M., "Libellus de Medicinalibus Indorum Herbis," Ms., 1552, Instituto 

Mexicano del Seguro Social, Mexico, 1964. 

(12) Eliade, M., "El Chamanismo," Fondo de Cultura Economica, Mexico, 1960. 

(13) Ruiz de Alarc6n, H., "Tratado de las supersticiones y costumbres gentilicas que 

oy viven entre los indios naturales desta Nueva Espafia," Imprenta del Museo 
Nacional, Mexico, 1892. 

(14) DEL Pozo, E. C, "La Botanica Medicinal Indigena de Mexico." Estudios de Cultura 

Nahuatl, Vol. 5, Mexico, 1965. 

(15) Reccho, N. a., "Rerum medicarum Novae Hispanie Thesaurus sen plantarum, 

animalium, mineralium mexicanorum historia ex EYancisi Hernandez . . .," 
Tipografia Vitalis Mascardi, Roma, 1651. 

(16) DEL Paso y Troncoso, F., "Estudios sobre la historia de la medicina en Mexico. I. 

La botanica entre los aztecas." Anales del Museo Nacional de Mexico, 3: 137-235, 
1886. 

(17) Wasson, G., "Notes on the present status of ololiuhqui and the other hallucinogens 

of Mexico," Botanical Museum Leaflets, 20 : 161-212, 1963. 



76 



Perspectives on the Use and 
Abuse of Psychedelic Drugs 



Daniel X. Freedman 

Department of Psychiatry, University of Chicago, Chicago, Illinois 

Page 



Introduction 77 

The Drug Mystique 79 

Scope of Contemporary Problems 80 

Inherent Problems in the Study of Abuse 81 

Inherent Problems in Ethnopsychopharmacology 82 

The Definition of a "Psychedelic" Dimension 85 

The Drug State and Its Consequences 86 

Some Features of the Drug State 86 

Immediacy, Novelty and Creativity 88 

"Cultogenic" Actions 88 

"Model Psychosis" in the Drug Experience 89 

Adaptations in the Drug Experience 90 

The Need for Synthesis 91 

The Role of Groups in Synthesis 93 

Use and Abuse of Conversion 94 

LSD in Psychiatry 95 

Abuse of LSD 96 

Motives for Use 97 

Summary Viev^r of the Value of Psychedelic Drugs 98 

References 99 



Introduction 

It has been remarked that tradition-bound scientists will predictably 
conclude that the proper use of hallucinogens is for research and medical 
application; the illicit abuse is for kicks and cults {69). Our puritanical 
ethics are said to prohibit us from even exploring whether the use of hallu- 
cinogens could improve the healthy, or possibly transform Western society 
into a Zen elysium. 

Whatever scientists may think, history does indeed record our unceasing 
urge to transcend limits and escape dreary reality or anxiety with the aid of 
magic, drugs, drama, festival rites, and (with biological regularity) through 
dreams. Even though we could doubt that drugs produce pleasure without 
the risk of harm, and wonder if man is built to sustain and to manage more 
than a brief chemically-induced glimpse of paradise, we must still examine 
the data of ethnology, pop culture, and clinical use for real evidence. Do 
such data indicate that there are drugs which specifically enhance these 
varied transcendent purposes ? If so, how do they, why and how exclusively 
or to what extent do they work and at what cost ? These questions will require 



77 



more explicit answers and more extensive research than we can presently 
report. 

To discriminate and analyze drug effects, quite imperfect tools will have 
to be borrowed from a variety of disciplines and contexts : from the social 
psychology of religion, of deviant behavior generally, of recreation, of 
social change and self-help movements, as well as the social psychology of 
aesthetics, pleasure and euphoria, and that of groups and of altered mental 
states. 

We should recognize that analysis of these problems occurs in the context 
of prevailing prejudices and publicity untempered by rational scrutiny. 
It already seems clear that whatever the motive for their use, the consequences 
of these drugs range from isolated aAve or benign or even bored surprise, to 
reported shifts of values to transient or occasionally long-term psychoses, to 
varieties of religious or aesthetic experience, and to clique formation and 
ritual. There are now conflicting reports of therapeutic efficacy in alcoholism, 
depression, character disorders and severe neurosis {2, 12, 19, 57, 62, 66, 
73, 79, 80, 82, 87). There is also a mushrooming psychedelic culture. This 
underlies the tribal motions (or brownian movements) of groups of long 
haired, barefooted dropouts, and the paraphernalia of fringe fashions, music 
and art — the trappings and trippings commercialized as psychedelic " go- 
go." Some serious theologians as well as our peripatetic prophets now seek 
the drugs as a promoter of love, of religious or self -enhancement [8, 21, Jf-Jj., 
83, 91). Some are sincere and private in these pursuits, some provocative 
and evangelistic. 

We are in any event presented with a barrage of elaborately literate 
(though not thereby the more accurate) claims. Of course, prophets, seers, 
gentle and ferocious reformers, acting for good or evil, have often held 
that special visions were not only their inspiration but their guide. They 
promise salvation. They also threaten misery to those who do not accurately 
assess (i.e., agree with) the efficacy of such claims. Truly dispassionate 
assessment — ^the exercise of judgment — may, as the elect warn, deprive one 
of access to the mysteries revealed in special states; thus if one is "in," 
there may be no way out ! The only answer to such dilemmas posed by any 
cult is exposure to experience, to knowledge and assessment over time — i.e., 
perspective. 

Thus these drugs are often used for a variety of purposes more complex 
than the simple pursuit of pleasure. In any event, hedonistic kicks can 
be achieved far more reliably with other chemicals or activities. If we take 
LSD as a prototype, I believe that in their extreme and most potent form 
we are examining drugs which influence that complex psychological ma- 
chinery with which we establish meaning and communion with others. There 
are few drugs which can so unhinge us from the constancies which regulate 
daily life, or so clearly present us with data from the "inside world" and 
from the many normally "inutile" perceptions potentially available to us. 
Surely, it is tempting to snatch some good from this. It also can do us 
little harm to place such experiences in the continuum of other states in 



78 



which a range of sensory impressions and insights revealed to the self are 
regarded with awe or claimed as therapeutic, or as personality if not world- 
transforming events (i, 5, 5, 56", 57, 67^ 80, 86, 88). Given an ample 
smorgasbord of effects, claims and usages, we can eventually best gain 
perspective by concentrating on what — if anything — is common to all of 
these varied drug effects. 

The Drug Mystique 

The young — who are being importuned by "friendly" advocates (and the 
young always have such friends) or lured by dire warnings — are entitled 
to what facts we now know about these problems. We in turn might learn 
from their interest, from not uncommon tragedies (of which we are seeing 
an increase) and ponder the adequacy of our responses to their probings 
and needs. My own patchwork impression of the growing use of marijuana 
and, to a lesser extent LSD, in intellectual groups is that these are hy and 
large more socially interesting (or irritating) than socially important phe- 
nomena. Rather, a drug mystique has been welded to the underlyingly serious 
shifts and strains inherently experienced by the most potentially unstable 
group of any society — the adolescent and young adult. That our society and 
our youth have problems is not at issue. Nor can we determine here whether 
indeed this generation is a "now" group, tending to confrontations, valuing 
honesty, love, direct and uncomplicated action, and avoiding ideologies in 
favor of simple justice; these values — however germane to the LSD expe- 
rience — were not born from the drugged mind. What is clear is that an 
ideology couched in the language of drugs or pseudo-zen philosophy has 
been insinuated into youth culture, and by a band of quite articulate writers 
and vagrant psychologists. These have replaced the old medicine show of 
yesteryear with an updated campus version complete with readings and 
alluring arguments, if not pills to sell : "drop out, tune in, turn on." Thus, 
this mystique has been generated by frenetic advertisements for themselves 
by the fad and fashion makers and idea mongers, and the press has been 
ready to exploit each sensation. 

The philosophical arguments of the advocates are carefully dissociated 
from the social consequences of their publications. They insist they have 
the civil right to take any agent which "does not harm others." Such claims 
gained their real momentum when a few psychologists who peddled the 
drug resented the notion that scientific and medical — or at least nurse's — 
training were required for responsible drug administration ; the requirement 
for such institutionalized "know-how" was viewed as a plot of a smug 
establishment. This argument, if carried to its extreme, would counsel a 
case requiring cardiac surgery to refuse care from a trained expert who 
votes Republican — and to do so, if necessary, on trumped up religious 
grounds. It seems ridiculous to have to state that while each of us in our 
infant development has attempted to assert the right to do what we want 



79 



when and where we want it, every society has shaped some constraints — 
ranging from some form of toilet training to traffic control — constraints 
impinging on our private views of our capacities, rights and bodily urges. 
Such is the uncivil level to which "debates" about the drugs lead I It is, of 
course, hardly a private matter (and it is a civil matter) when such prose- 
lytizing leads to a number of drug-related cases requiring medical and 
psychiatric care for brief or longer periods of time. 

The irresponsibility of the psychedelic gurus is demonstrated in the fact 
that while they advertise the drug as only a part of tTieir version of a way 
of life, they are not in a position to manage the consequences of their ideologi- 
cal schemes. Can they really be- innocently surprised if the drug per se is 
more alluring and interesting to the immature than their philosophical 
preachings ? They may reach certain segments of our youth far more read.ily 
than most conventional authorities, but nothing in their performance to 
date shows they know how to manage or anticipate what they so blithely 
initiate. Psychiatrists who have worked intensively in private institutions 
with young borderline or schizophrenic patients are quite familiar with some 
of the tribal behaviors, excesses, philosophizing, and "freak outs" similar 
to those which occur in psychedelic cults. "Wild analysis" and "psyching" — 
probing into one another's supposedly tmconscious motives — characterized 
youth of previous generations, as did self-experiments with hypnosis even 
in the 19th century. 



The increasing problem of drug abuse in most countries is alcohol, followed 
by barbiturates, amphetamines, opiates and mild tranquilizers. As I see it. 
the consequences to national health and social welfare of these drugs are not 
as yet startling — either in terms of the utility of LSD o?' its harm. Debates 
about whether to use or not to use LSD are hardly as consequential as the 
use of "The Pill" in our society. The agent most frequently used by youth 
for illicit purposes and with lethal effect is the automobile: and the most 
faithful monitor of the scope of such social problems is the prevailing high 
insurance rates for young males. I know of no rate changes for medical, 
psychiatric or mortician's coverage which have been instituted by this actu- 
arial superego of our society in response to these chemicals. This is an 
interesting generation but they have not yet gone completely to pot ! On 
the campus scene, interest in these drugs clearly flies high, but not in the 
majoritj- of students. "Acid" commentaries are, if not more abmidant. more 
influential than trips. While in the large picture, the scope and pattern of 
hallucinogenic drug use in our society must be said to be more sensational 
than consequential, the development of cults and a sharp increase in drug- 
taking behavior in relatively small, often elite or fringe segments of our 
society warrants investigation. 




Contemporary Problems 



80 



Inherent Problems in the Study of Abuse 

For opiate use and abuse and for the abusive potential in marijuana (j^, 6^ 
13^ 16, 16, Jfi, 60, 61, 63, 68) , excellent studies have been done. Designs for the 
study of LSD abuse could profit from these. It is clear that the motives 
for experimenting with a drug, for trying a drug, for interpreting the subjec- 
tive effects of a drug {81 ) , and for continuing drug usage and for seriously 
maintaining it can be quite different. The ability of the habituated to control 
their intake also varies ; e.g., many people have the alcohol habit but control 
their intake in accord with their social obligations. It is also clear that the 
population of users shifts; e.g., cannabis users have shifted throughout 
history even in countries such as India, and before 1910, middle class women 
were frequently represented among our opiate addicted population. The 
response of society to drugs differs, often mecurially and rarely in response 
to sober judgments. For example, over 30 years ago, the Federal Nar- 
cotics Bureau saw no harm in marijuana and within 2 years — and with 
no more objective data — decided there was a menace. The complexities of 
the drug-taking, drug selling and drug policing groups (who form sub- 
societies "needing" each other) , should be noted. When underworld vendors 
specialize in one class of illicit imports, they may also market others. Thus 
heroin and marijuana are occasionally though not usually sold by the same 
peddlers. This association is a social consequence of prohibition and polic- 
ing — not an actual or pharmacological link of the drugs. Marijuana users, 
psychedelic drug or opiate users, "goofball" or amphetamine abusers, are not 
commonly the same population (although there is overlap), nor has the 
illicit «3upply of psychedelics yet been merged with that of heroin. 

For the nonaddicting but so-called hallucinogenic drugs, we have much 
yet to learn about current practices. Only a minute fraction of persons who 
have taken these drugs could be said to constitute a reliable base for study 
of long-term users ; groups of persons who drift in and out of the category 
of users are not easy to identify, and are hardly reliable reporters since some 
are always first discovering the drug while others are experiencing disillusion 
or worse. Indeed, over the past ten years we have been greeted with fresh 
pronouncements of new discovery of the effects of a synthetic compound 
(LSD) which has recurrently startled its takers since it was first known — 
well over 20 years ago. Scrutiny of the response to the mescaline-containing 
peyote — known since the last century — similarly reveals cycles of startled 
amazement as several new groups or persons came to learn of it and adapt to 
it; e.g., Havelock Ellis and William James (who did not, incidentally, form 
cults in 1902) {28,30). 

Complications for research arise from the current publicity. Selling and 
propaganda create a bandwagon effect and complicate a sober assessment 
of the extent and nature of drug use. The hucksters gain attention, audiences 
and monetary support as they threaten the establishment with love and^ — 
long before the fact of truly increased drug usage — announce that hordes 
of young people are, if not their followers, then independently dedicated 
drug users. The establishment, on the other hand, must react with irritation 

81 



or even fright at the announced threat. The head of the Food and Drug 
Administration has a political hide which can be at stake since he must 
answer to readily alarmed legislators — not to research scientists. Accordingly, 
those scientists studying the effects of drugs on brain chemistry and behavior 
in animals have clear-cut procedures, for obtaining and accounting for sup- 
plies of narcotics but not of psychotomimetics (in spite of the promise by 
the FDA in May of 1966 to set up machinery and explicit guidelines). 
Finally, as the advertising escalates and the empirical problem grows, the 
young and their parents must enter the debate and assess the claims of value. 
Physicians hysterically crying alarm rather than pointing rationally to 
danger join the melee. The use of these drugs in experimental psychiatry to 
study altered states or the genesis of symptoms or new learning or the nature 
of brain mechanisms related to altered perception {10^ 29, 52, 58, 72, 93) 
proceeds with National Institute of Mental Health support, but not without 
severe problems of sanction contingent upon sensationalism and fear in the 
bureaucracy. 

Physicians who make headlines with reports of dire results both lure the 
susceptible and generate their clientele who are latently worried about what 
they are doing. Sober medical assessment would be more effective — and 
honest — as a deterrent. It is also most important to sort out the various 
factors which might complicate the picture the physician sees when patients 
are brought by drugged friends or in other disorganized circumstances to 
hospitals for one or another indication. The possibility of complicated drug- 
taking patterns in such patients, of prior instability if not mental disorder, 
is to be investigated. In brief, the fact that the drug is a precipitant or 
concommitant of an ongoing disorder must very clearly be distinguished 
before we determine anything really definitive about long-term effects 
{22, 23, 2U, 31, 32, k2, 1^5, 61^, 77, 92) . If we recall the reaction of the medical 
community to the psychotogenic effect of steroids, and if we take cognizance 
now of the fact that these disorders still occur, the difference is that we now 
know what the steroid psychoses portend ; we can predict with more confidence 
what the results will be and accordingly (even though attending physicians 
are often uncomfortable) there is little scare literature presenting uneval- 
uated snapshots of steroid psychoses in cross-section, so to speak. As a gen- 
eral public we are gullible, vulnerable to sensationalism and to over-reactions 
on any side of the issues involving behavior active drugs. This is true also 
not only of the press, of poets genuine and manque, but of legislators, 
bureaucrats, and physicians. 

Inherent Problems in Ethnopsychopharmacology 

We react with similar responses to a variety of drug-induced experiences, 
but there are characteristic behavioral patterns and social uses which cluster 
around one or another drug ; e.g., opiates probably do differ not only pharma- 
cologically and psychologically but in terms of patterns of social use from 
LSD or peyote. Research is required both at the psychopharmacological and 



82 



ethnological levels to be certain. A major problem exists anytime we study 
the varieties of so-called irrational behavior. This is that there is nothing 
intrinsic to the training and practice of a wide number of professionals 
which equips them knowledgeably to handle and interpret either the irra- 
tional itself or themselves when dealing with it. What little knowledge re- 
sides within the experience of psychiatry has not been made sufficiently ex- 
plicit to be extensively applied by others. If a historian documented the dis- 
tractions inherent in trying to understand or deal with schizophrenia, with 
hypnosis, with dreams, or with such questions as religious conversion — and 
certainly with cannabis and LSD — we would see that it has not been easy 
for men to comport themselves with the best of rational, let alone scientific 
skill in these areas. Judgments and assertions, then, have to be continuously 
assessed. 

The sorting of the intrinsic patterns of drug effects from their varied elabo- 
rations presents difficulties. For example, the social use of a drug cannot tell 
us infallibly about the basic pattern of its effects. What Barron, Jarvick and 
Bunnell (5) called "drug-induced ego disruptions" refers to a wide range of 
substances which can provide a change of scene, a moment of being out of 
it, a holiday from the constrictions of reality. A wide variety of agents can 
shift our normal engagement with the world, producing an altered state. This 
state in intself may promote the release of effects and be welcomed for its 
novelty value as a remarkable trip from reality. Etched upon it may be a 
specific pattern of the drug. I believe that LSD extends and accents this 
primary ego state in a salient and sustained way. 

A second complication is that sufficiently strong motives can capture any 
opportune occasion in order to generate uninhibited or cultist behavior. 
Thirdly, in case a cultural pattern of drug effects seems at first glance invari- 
ant, the powerful role of set and setting should be assessed ; for example, the 
exclusive "Mexican-ness" of Hoffman's visions when he first ingested psilocy- 
bin (derived from a Mexican mushroom) is hardly ascribable to a specific 
chemical action. 

Pharmacological factors such as dose, route and dosage schedule, and the 
form and preparation of the active agent are also critical. For brevity, can- 
nabis can be taken as an example : by and large, the more potent the prepara- 
tion — the more concentrated the form of the resin — ^the more psychedelic or 
psychotomimetic the effects. Panic states, temporary psychosis and paranoid 
episodes similar to those observed currently with LSD, occur more f reqeuntly 
with the more potent preparations illicitly available in India {16, 17) and 
the Near East (7) . Many abusers in Morocco and India are found in settings 
not unlike our alcoholic skid rows. The weaker marijuana used here has dras- 
tically fewer such effects. Inhalation or ingestion alters the intensity of effects 

The pattern of use of LSD is determined in part by the dose-dependent 
tolerance induced {39, 1^7, 95) . Three or four days are required for its full 
development or its full loss : daily dosage leads to dramatically diminished 
effects unless the dose is considerably increased. "Cyclicity" in tolerance {53) 
is seen with higher daily dosages; e.g., tolerance is lost and regained with 



83 



every eighth or ninth consecutive daily dose. After a single dose there is 
"psychological satiation," as McGlothlin calls it, which is characteristic for 
any single LSD experience : one dose is emotionally sufficient, if not exhaust- 
ing, for most people for quite a period — days, or weeks, or years. 

If we wish to discern some universally basic pattern of effects {37), we 
also have to consider at what level drug effects on behavior can intrinsically 
be analysed. Dubos {27) , expressed the fundamental notion that even a highly 
selective drug would react with some structure other than the one for which 
it was designed ; absolute selectivity for effects is a chemical impossibility. 
This does not mean that there are not intrinsically discrete chemical controls 
or that chemical reactions within cells are not under exquisite feedback regu- 
lations, but the control of integrated sequences of behavior remains a complex 
problem. Yet, in view of the surprising associations and dissociations of 
which the nervous system is capable (for example, phenothiazine-induced 
sedation in the presence of motor excitation) it is not inconceivable that 
chemicals exist which can produce desirable modifications in components of 
the pattern of effects of a drug such as LSD. The fact that the indole and 
catechol derivatives which are psychotomimetic induce a response in brain 
(altering brain serotonin metabolism and probably increasing the utilization 
of norepinephrine {33, SJf., 35, 36, 38, J(3) , that most of these show cross toler- 
ance, and that agents — such as atropine or Ditran — producing'a deleriod type 
of response {33, 58, 93, 94-), affect brain acetylcholine indicates that we are 
dealing with agents for which some exquisite biological specificity exists; 
indeed this is the basic reason for scientific interest in the mode of action of 
the drug, a search that could lead to critical neurochemical mechanisms. Each 
of the brain monaamines appears to be lawfully related to specific, largely 
polysynaptic neural systems and it is not unlikely that with autoradiography 
{90), and fluorescence and electron microscopy that our knowledge of the 
involved neural systems and chemical changes induced by these drugs can be 
more finely specified {33, 38). 

Finally it will be noted that most of the drugs mentioned in this conference 
have had multiple therapeutic usages, from carbuncles to mania. The Navaho 
clearly seek the cure of all manner of both physical and psychic ailments 
with peyote. This fact means that the ethnologist must be wary of the extent 
to which reported effects are specifically drug related. The distinction be- 
tween symptoms of organic dysfunction and those of bodily discomfort in 
various psychic states is never easy. We see this confusion in small children ; 
there are quite probably differences in social classes, personalities, and cul- 
tures in the extent to which the body becomes a "sentient referent" for the 
consequences of social and personal anguish. This surely could lead to con- 
founding reports of drug effects. 

Apparently where drugs can disrupt normal ego functions they can com- 
prise a polytherapeutics for the so-called functional factor in illness. How 
this is accomplished is not clear; perhaps through an ultimate shift of 
attention as in hypnosis ; or through the effects of powerful wishes for cure — 
which observably dampen anxiety. Something as nebulous and as potent as 
faith and confidence is involved. Wlien we ingest a drug because of anxiety 



84 



or weakness, there is a monotonous regularity in the "non-empirical" inter- 
pretations which may be evoked; psychologically, the drug is seen as a 
power, either one evoking terror (poison or devils) or one producing sexual, 
physical or spiritual strength leading to salvation or healing. Accordingly, 
in reviewing the folk usages of drugs for therapeutic clues and in obtaining 
discriminative information on the effects of drugs on patterns of behavior, 
we have to distinguish the general range of effects of ego disruption and 
what is commonly called the power of suggestion. Doing so, we can more 
confidently focus on what is specific about the so-called hallucinogenic drugs, 
including the ways in which they do and do not enhance suggestion. 

The Definition of a "Psychedelic" Dimension 

Comparative psychopharmacological studies of the various potent drugs 
would lead to a better appreciation of the fundamental dimensions of behav- 
ior, of the ground out of which complex but related behaviors emerge. That 
element contributed by specifiG drug effects to the entire picture of drug 
usage will require more focus. Given such reservations, it seems that the 
recurrent theme in historical records is that certain drugs are compellingly 
related to learning, to self-revelation, and that they are involved in some 
mystical, often ritual, use. McGlothlin notes that the American Indian often 
states that "peyote teaches." He does not find this major theme running 
through accounts of marijuana usage [69). Again the potent preparations 
of cannabis are an exception and the milder preparations have been used to 
enhance contemplative states as well as for a "high". Apparently, there is 
a continuum of effects along the dimension of self -revealing and ritual usages. 

To the extent that there are classes of agents which starkly reveal some- 
thing about the depths or the dimensions of the mind — exposing these dimen- 
sions to our attention — we can say that both use and abuse stem from our 
amazed response to the subjective experience revealed by these drug states. 
If this is what Humphrey Osmond meant by the term "psychedelic" or 
"mind manifesting" for drugs such as LSD, it is an apt though not novel 
description. There is a wide range of contexts — including clinical disorder 
in which states of heightened awareness with varying degrees of mental 
clarity occur, and a variety of initiating causes. The mode of functioning 
and experiencing called psychedelic reflects an innate capacity (like the 
dream) of which the human mind, in a general sense, is capable {10) . The 
fact that a certain class of drugs so sharply compels this level of function is 
what so intrigues the behavioral scientist. 

A rather famous and wordy Harvard professor noted that drug-induced 
intoxication "expands, unites and says yes ... it makes . . . (man) for the 
moment . . . one with truth." William James {JjS) went on to write that parted 
from normal consciousness "... by the flimsiest of screens, there lie potential 
forms of consciousness entirely different . . . apply the requisite stimulus 
and at a touch they are there in all their completeness . . . somewhere (they) 
have their field of application and adaptation. . . . How to regard them is 



85 



the question . . . they may determine attitudes through they cannot furnish 
formulas and open a region though they fail to give a maf!''' (Italic mine.) 

Many authors have stressed that the human mind is apparently built with 
mechanisms for constancy with which to structure and use these fluid and 
irrational components. Indeed in the most systematic series of neuropsycho- 
logical drug studies extant — those of Heinrich Kliiver (5^) with mescaline — 
the author concludes with speculations about the drug's differential action 
on those subcortical areas of brain which are characterized by emotionality 
and variability and those anchoring sensory-motor systems which aid in 
constancy. The question perhaps is not so much expanding the mind — it is 
expanded enough — but to see if there are drugs which can enhance a better 
and more creative coordination among these so-called regions. 

The Drug State and its Consequences 

So whether we set out on a personal or on a scientific research effort to 
discover and explicate this order of the mind, whether we examine it by 
introspection or examine its effects on natives, patients and others, we embark 
on a search which is intrinsically difficult and fraught with misunderstand- 
ing. One can expect nothing else if we attemj^t to deal with the irrational. In 
any event, we shall try to describe a multipotential state which, in its most 
general sense, can underwrite a variety of outcomes : religious feeling and 
conversions, states of hyper-perception leading to inspirational insights, to 
psychosis, to exalted states or to behavior or value change. 

The more we can grasp some of the intrinsic features of this state, the more 
we will be able to understand some of its variable outcomes. So if we had 
little experience with drugs, we might still be able to predict their con- 
sequences and understand, for example, why these drugs might be properly 
called, among other ascriptions, "cultogenic agents." Some of the modes of 
experience — the styles — which characterize the drug experience seem fre- 
quently to be linked to the outcome or to the style of life commonly 
centered around drug taking: whether this "hang-over" of drug effects 
is learning or reinf ormement of the ongoing trend of goals and adaptions, 
or based on more complex variables and mechanisms is not known. 

Some Features of the Drug State 

The sequence of effects following the usual doses has been described 
elsewhere {4-S, 78) . During the first four and half hours there is generally 
a clear cut self recognition of effects — an internal "T.V. show" which is 
followed by another four or five hour period in which a subjective sense 
of change is not marked but during which heightened self centeredness, 
ideas of reference and a certain "apartness" are observed. At 12^8 hours 
after drug ingestion there may or may not be some let-down and slight 
fatigue. There is no craving for a drug to relieve this if it occurs and no 



86 



true physiological withdrawal, as is the case with opiates, alcohol, sedatives, 
and certain tranquilizers. 

It is the intense experience without clouded consciousness — the heightened 
"spectator ego" witnessing the excitement, which is characteristic for these 
drugs in usual dosages. Thus there is a split of the self — a portion of which 
is a relatively passive monitor rather than an active, focusing and initiating 
force— and a portion of which receives vivid experiences. Some people 
seem to repeat this long after the drug state; standing apart from life or 
relying on the group to direct events, they turn away from the prosaic 
world — or else are turned away by society, as well as turned on by the 
drug. They may find a clique or a group which tolerates this disposition. 

During the drug state, awareness becomes intensely vivid while self- 
control over input is remarkably diminished ; thus there is the lurking threat 
of loss of inner control — loss of control of integral stability — of the "dying 
of the ego" so often reported in bad trips or in phases of mystical experiences 
with the drug. In the drug state, customary boundaries become fluid and 
the familiar becomes novel and portentous. Events take on a trajectory of 
their own; qualities become intense and gain a life of their own; redness 
is more interesting than the object which is red; meaningfulness more 
important than what is specifically meant ; connotations balloon into cosmic 
allusiveness ; the limits of sobriety are lost. The very definition of the 
importance of the external world shifts when most mental activity is absorbed 
either in monitoring the novelty of experience or in maintaining the integrity 
of the self. And, after the drug state, we may find more tolerance for 
ambiguity and a diminished readiness for the quick answer; we also caji 
find an associated inability to decide, to discriminate, to make commit- 
ments. Spindler reported the latter as a Rorschach pattern in certain Indian 
peyote users (SO). Such a tendency to avoid distinctions could lead to 
alienation and retreatism, even if these were not pre-existing traits (as they 
often are) . A certain isolation, or sense of it, tends to occur as a trait in many 
drug experimenters ; the after-effects may emphasize the pre-existing traits. 
For many the drug experience may represent a beginning which without 
luck or expertise, cannot easily come to a useful conclusion; neurotic acts 
also have been viewed as misguided attempts at self cure. Thus many reported 
immediate after effects of LSD — both good and bad — could depend largely 
on the motive for taking the drug and in fact could be transient rather than 
transforming. 

In any event, when portentous implications and hidden meanings per- 
petually contaminate the response to the explicit signs and conventions 
of everyday life, "focus" and goal directed efficiency are usually impaired. 
Since judgment is not enhanced during the drug state and since isolation 
or apartness (even when sanctioned by a minority group) bring their own 
problems, it is clear that persons who continually overvalue the modes of 
experience of the drug state could develop patterns of poor practical judg- 
ment. The consequences of long-term and frequent use of the drug — involv- 
ing probably 5-15 percent of those experimenting with LSD — would prob- 
ably have to be evaluated in this context. 



87 



Immediacy, Novelty and Creativity 

In the drug state, the experience of compelling immediacy diminishes 
the normal importance of past and future. One's organized anticipation 
of time dissolves (which may incidentally be why, when properly given, 
the drug can replace narcotics in dying cancer patients) . It also is related 
to the overvaluation of "nowness," the fickle pursuit of the novel apparent 
in certain youth subcultures {76, 84-). The ability to see old and familiar 
events in a new light is a facet of the shift in organized anticipations and 
equally a facet in the poorly understood processes related to creativity. The 
impairment of goal directed efficiency also carries with it the impairment 
of integrative and synthetic functions and abilities. Thus the mere mergings 
of sensory objects (the synesthesias, the plastic rearrangements or the clear 
focusing upon fine details or usually disregarded elements) is hardly the 
same as an organized building and arrangement in which "boundaries" are, 
at some jimcture, essential. Creativity requires some use of the drug-induced 
facility for seeing new meanings ; but there is nothing about the drug effect 
which specifically enhances this synthetic and organizing facility. Indeed 
as we shall stress, the need for synthesis — ^not the ability to synthesize — is 
what is enhanced in the drug state. 

"Cidtogenic" Actions 

An important feature of the state is an enhanced dependence upon the 
environment for structure and support as well as enhanced vulnerability to 
the surrounding milieu. With the loss of boundaries, persons or a group are 
used for such elemental functions as control — for helping one to know what 
is inside and what is outside, for comfort and for binding and balancing the 
fragmenting world (10). When one is absorbed either in monitoring the 
novelty of experience or in maintaining self integrity the major changes in 
the external world will be overlooked or slight changes will assume a critical 
role. Persons or objects in the environment have positive or negative value 
in terms of quite elemental functions : e.g. as threats or as anchors in main- 
taining control (quite as in the so-called psychotic transference) . Persons are 
self-centeredly seen as objects — not to be related with nor evaluated in their 
own right — but either to be clung to or to be contemplated in terms of what 
essentially is a self centered, esthetic or ideologic frame of reference. At 
best this narcissistic reworking of one's relationship to others and to one's 
own ambitions can lead to outcomes which are socially valued — wisdom, 
humor, perspective — but such internal syntheses never guarantee socially 
pleasant behavior (e.g., non-competitive behavior or conduct which takes an 
ideal regard for others into accoimt (54). In other words, the claims for a 
different perspective have to be evaluated both in terms of how this is 
integrated in the life and in the internal rearrangements of values of the 
user; one need not argue with the asserted shift in values (although even 
this can be monitored (72) ), but the consequences of this can be assessed. 



88 



Thus with the dissolving boundaries of self and outside, with the fusion 
of self and surroundings some of the strain between harsh authority and 
personal strivings can for the moment be transcended or dissolved. At the 
same time there is a leaning on others for structure and control and hence, 
when the drugs are taken in a group setting, the breach with reality repre- 
sented by the drugs can be filled by the directive mystique and support of 
the group. This is, in part, why I have termed these drugs "cultogenic." 

"Model Psychosis" in the Drug Experience 

The elements of a model psychosis are present. By model we do not 
mean identity; rather we mean an approach to certain processes which are 
present to some extent both in the drug state and psychoses ; the conditions 
for either state have similarities and obvious differences (just as do dreams 
and psychosis (4-^)). For example, what is impinging on an ongoing per- 
ception is a vivid memory of what has just been perceived ; these co-existing 
images can compete for attention and thus give rise to illusions. These can 
be immaginatively elaborated into hallucinations. Similarly, past memories 
can emerge vividly, competing for the status of current reality. The failure 
to suppress the prior perception or memory or thought characterizes what 
Bleuler called "double registration" in schizophrenia or what, in Rorschach 
parlance, is called contamination. Similarly the failure of identities and cate- 
gories to be maintained underlies most of the descriptions of paralogic in 
schizophrenia. The capacity to direct one's focus is impaired; allocation of 
the source of a feeling, a sound, a sight, or a thought becomes difficult since 
inside and outside become fused. Accordingly there are frequent "projec- 
tions" or misconceptions of motives. This tendency is reinforced when one 
must exercise energy to account for slight changes in the environment. It 
of course bears upon our thinking about any psychosis to recognize that pri- 
mary or secondary shifts in the elemental ego functions of discrimination 
underlie a range of symptoms. 

Similarly effects can be enhanced under the drug state but are difficult to 
specify since several contrary feelings co-exist or fluctuate — reminiscent of 
ambivalence. Thus euphoria mixed with tension may be seen. Laughing and/ 
or crying in the first three hours are not uncommon. Subjects later refer to 
the total state as a pleasant-unpleasant experience. However these expe- 
riences are represented, they are evolved from a ground work entailing a 
co-existence, heightening, and fragmenting of component urges and feelings. 
With care, one observes that preceeding this there is a primary need for 
elemental tension-discharge — a welling up which requires laughing or crying 
for relief. Subjects have to laugh or cry and they then seem to find the 
appropriate setting to rationalize this ; the cognitive and structural aspects 
of affect seem to follow the need for discharge. 

Thus the enhanced value and intense attention placed on the self, the 
"double registrations" the ambivalence, heightened tension and diminished 
control all can represent the primary symptoms of a psychosis. The appear- 
ance of peak experiences (or acute psychedelic experiences) in psychosis has 

89 

262-016 0-67— 8 



long been documented (7(9, Ifi^ 67). Thus we have with these drugs at least 
a tool with which to study the genesis and sequence of a number of familiar 
phenomena in psychiatry. Whether this can lead us to a better sorting and 
description of the varied elements which are present in the range of clinical 
disorders is yet an unanswered question; it is for example, obvious that 
differences in outcome of LSD states depend upon specific prior strengths as 
well as varying circumstances. These various elements may also be relevant 
in the phenomena and outcomes we encounter in clinical psychiatry. 

Adaptations in the Drug Experience 

Some persons endure all this without evident harm. The spectator ego can 
simply be interested in the reversal of figure and ground, the visual tricks, 
or — with higher doses — the spectator is entranced or totally absorbed. The 
experiencing ego can — especially with increasing dosage — be overwhelmed. 
At any level, defensiveness can appear; the spectator shuts his eyes and a 
blind struggle for control may dominate. There are different modes of cop- 
ing with the drug state which could be called protective. One protection is 
not to fight the experiences during the drug state. An upsurge of the tradi- 
tional defensive operations may lead to temporary panic even in relatively 
stable people. This has been reported both in the LSD and peyote cults, and 
has been observed by medical therapists. 

Most people working with the drug (either licitly or illicitly) note that 
unstable surroundings or confused motives may lead to "bad trips." The 
attitudes under which the drug is taken are important. The Indians of the 
Native American Church emphasize sincerity, and the desire to learn, and 
they link bad peyote experiences with the presence of aggression and com- 
petition rather than the setting of sincerity and brotherly love and a willing- 
ness to learn. It is striking that when self examination or confrontation 
with internal problems is the motive for drug-taking, effects are sometimes 
bad. When problems are aptly externalized or shared there is less panic 
and subsequent upset. Thus a certain yielding and surrender of ambition 
and personal autonomy helps some individuals to have a good experience, 
but this requires if not group support a certain personal strength, or at 
least a facility. It also requires stable groups. 

Some people achieve an overall stability by a disposition to react with an 
astounded pleasure to the whole flux of events. Others are encouraged or 
equipped to transcend the fragmented disparate elements, letting them flow 
into the sway of a mystique, or letting them be steered by latent guiding 
interests or memories. Thus all that occurs is given a tone — or a very diffuse 
direction. With higher dosages and the increasing loss of the capacity for 
detailed focusing, the importance of guiding "sets" (music, mystique, af- 
fective expectations such as the doctrine of boundless love) is enhanced. 

The drug experience is compelling and hard to convey but incredibly vivid, 
and the extent to which the experience of a specific "trip" is related to out- 
come requires finer study. So too does the fact that one good trip does not 
predict a second. Nevertheless the primary changes are the background 



90 



state from which a number of outcomes and adaptations ensue — adaptations 
hoth during and after the drug experience. No doubt the rearrangements of 
reality which occur during this state produce a memorable experience, but 
one is reminded of Sidney Cohen's remark that most people get what they 
deserve or what they are equipped at the time to experience as modified by 
set, equipment and setting {21). 

The Need for Synthesis 

Anyone who has experienced this intense episode must come to deal with 
it. Our dreams also are an episode in a sequence of states which we usually 
can somehow integrate into the normal fabric of living ; similarly something 
must now be done with the total drug experience — nightmare, illusion or 
ecstasy. Some borrow stability from ready-made explanations. Still others 
will decide that the sense of cosmic comprehension is equivalent to mastery. 
They will tend to deny the anxiety about the loss or potential loss of control. 
In any event, when such a profound breach with normal functioning occurs, 
there is some need to synthesize and integrate this experience, to represent 
and to cope with it in some way. 

Some individuals will isolate it; some will set it aside in an attempt to 
master it and still others, lacking any other means of mastery, will be com- 
pelled repeatedly and unexpectedly, to confront what was experienced. We 
see this in students who come in for help weeks after a trip. 

In others the breakdown of those constancies and habits which normally 
smooth over the disparate details of our perceptions and actions can persist 
in benign ways. One scientist experienced his peripheral vision to be en- 
hanced during the drug state ; it is not uncommon that there is an equivalence 
of value for what is at the periphery and what is normally perceived at 
the center of the virsual field. He commuted daily, reading during the trip. 
For months after the drug, he was bothered by the telephone poles which 
flashed by his train window. He could no longer suppress what normally 
is background rather than a compelling figure. Similarly, the unconscious 
"background" to thoughts and feelings can emerge. (There are numerous 
anticipatory sets or constancies which operate to keep the body oriented in 
space and ready to meet the environment as we expect to experience it; 
the mind provides constancy wherever the sense organs deal with variability. 
We anticipate or correct for the images on our retina to keep the world 
stable and ordered; the hand stretched 8 inches before one, may appear 
small though on the retina or camera it is large. Coming off a boat one may 
still waddle anticipating the roll of the ship.) LSD appears to affect such 
perceptual anticipations and more complex regulatory systems. It rear- 
ranges our ideas of order. It is striking that prior to psychedelic ideology 
and experiments with self-therapy, mescaline produced more "perceptual" 
than self-revealing experiences, but the mode of breakdown of constancies 
is similar whether the self or perceptions are a referent. 

The intensity of the drug experience manifest in the change of con- 
stancies can lead to a number of repetitive behaviors. Gordon Allport noted 



91 



that, once the vividly religious state is experienced, one seeks throughout 
life to recapture its inspiration (3). The search for synthesis may take the 
form of attempts to re-experience the intensity of elements within the drug 
experience in order to master it. The classic example, of course, is the trau- 
matic neurosis in which, following a traumatic episode in the trenches, the 
soldier recurrently dreams the nightmare — apparently in order to master 
it. This has been noted in every major theory of psychopathology since 
the 19th century. The hypnoid state described by Breuer was one of two 
causes which he and Freud offered for mental symptoms. Put simply, in a 
state of altered consciousness where control over awareness is diminished, 
there is no way to bind the intensities experienced and symptoms may ensue. 
Similarly, in growth and development, many bits and pieces of impressions, 
many intense experiences — experiences which for the child are intense — 
have to be organized in the ongoing stream of developing psychological 
control, and often this fails. 

Repetitive symptoms — such as acting out — may be viewed as misguided 
attempts to give structure to these pre-verbal impressions and intensities — 
to restore or find constancies and boundaries. Some experience a "loss" mani- 
fest by depression and an urge to recapture the illusionary world of the drug. 
We know that people may produce vivid consequences or experiences in order 
to see them in a new light. These are experiences which are presented to con- 
sciousness, but what often is lacking is the element of guidance, correction, 
reflection and structure which leads to authentic self-mastery ; this may be the 
chief source of danger of LSD — the lack of structure and autonomy and the 
traumatic and potent intensity ! 

Thus acting out behavior with or without a drug often compels control, 
correction and guidance, and appears as a provocative accusation against 
authority. The young do not merely "turn on" themselves but seem to display 
great anger at the guides whom they feel failed them (indeed the prophets 
counsel students to "turn on" their parents — one of their metaphors which 
is most likely not to be concretely interpreted) . Displacing the total experi- 
ence and the anxieties inherent in it by attacks upon the establishment, they 
thereby keep a link — and a very strong one — to the very strictures which 
had previously absorbed them (just as a misbehaving child is tied to his 
parents by evoking their involved irritation or punishment). Others show 
delayed panic, depression or anxiety, and seek out friends for help, and still 
others aggressively talk about their experience as if they were trying to put 
it together. Some kind of continuity with the gap in reality is sought for. 
The bridge may be a book as it was with Huxley, a silent synthesis or change 
of values and tastes, or the understanding of a group or person. In the 
Native American Church, the Indian utilizes all these elements — religious 
explanation and adherence, specific ceremonies and the group with its ide- 
ology — to integrate the experience which serves a purpose in the total fabric 
of his life. It has been speculated that during the ceremonies, by borrowing 
the strength of "father peyote" and experiencing an enhancement of self, he 
transcends personal anxiety and inadequacy. Some sects are tutored to ignore 
the visions and disparate elements of the drug state to achieve this higher 



92 



cosmic state. The Indian does not accordingly seek a simple "high" or thrill 
with the drug (i, 66, 86) . 

For some, denial of inadequacy and enhanced omnipotence — delusional 
autonomy — may lead to various outcomes : that of the benevolent and foolish 
prophet, or the defensive, alienated therapist, angry at those who prevent his 
curing the rest of the world. Indeed we must seriously wonder why those 
who find salvation are so generous and so ready to proselytize and adver- 
tise ! Implied are unsolved problems with authority figures. In any event it 
appears that salvation often involves renunciation of previous ties and 
that those who are saved must repetitively convince others in order to dimin- 
ish their own doubt, isolation and guilt. At best, they may do this in order to 
reachieve union with those with whom they have been separated by their 
unique vision and experience, and to synthesize these breaches with important 
others. 

The Role of Groups in Synthesis 

We have referred to the strain between the exertion of personal strivings 
for autonomy (i.e., needs to order reality and influence the world) and in- 
ternal authority (the voice of conscience). Certain groups seem built to 
absorb this strain. Many successful self-help groups appear to be peer groups. 
With such arrangements the distance between authority and the miscreant 
(reminiscent of that between parent and child) is diminished and so too is 
the inner tension. The cost is a surrender of certain order of autonomy to the 
group and dependence upon it. It may be less painful to drop pretense and 
to permit less masking of inadequacy in the presence of uncritical and non- 
threatening peers. Of course there may also be a tendency to externalize the 
conflict with authority, a tendency reinforced by peer-grouping. Still this 
can permit authentic self involvement at a level which is realistically avail- 
able to the persons involved. 

Ideally, autonomy and involvement might mean not to be distracted by 
arguments with authority ; such terms should connote putting oneself in the 
place of authority — not imitatively — but in terms of real commitments in- 
volving risk, initiative and responsibility. To some extent self-help groups 
can aid members to move in these directions. Yet, such adjustments mean 
relying heavily on the concrete presence and reinforcement of a sane group 
which shares the burdens of initiative. This is not always achieved. In some 
chronic users one sees a bland impulsiveness — an indifference to the habitual 
and customary which may border on a supercilious posture of superiority. 
The elect of many cults either assume the attitude or the outsider feels this to 
be the attitude of those who know something he does not. This posture has 
also been remarked upon in the American Indian peyote users, although they, 
too (as with the Navaho), are often subcultures not infrequently at odds 
with established groups and leaders (1 ) . 

Group sanctioning of the drug state can diminish the intensity and isola- 
tion ; the group mystique tends to give integration through a credible rendi- 
tion, if not sanction to events which by their very nature cannot easily be 



93 



translated into public language. The mystique may not be more descriptive 
of the drug state but simply apparently precise and sufficiently allusive to 
serve as a representation of and compensation for the breach with reality. 

Mystical or religious representations also are remarkably apt for synthe- 
sizing the experience. Religion relates man to his limits while taking account 
of his boundlessness ^vhich occurs in all aspects of this realm of the mind. 
It may be that religious symbolism aptly represents the transformations 
characteristic of this latent part of the mind. Against fragmentation and 
directionlessness something coherent lends continuity to experience. Against 
dread, transcendent love can prevail ; loving like redness can apparently be 
enhanced and is remembered. The "lovingness"' and "strongness"' of a parent 
can be parted from the particular persons and transcendentally represented 
in various forms of power ascribed to deities. 

Use and Abuse of Conversion 

There are, then, a number of features of this multipotential state related 
to its intensity, its novelty, its boundlessness which account for some of the 
expectable occurrences within it and some of the expectable — and observed — 
dangers and outcomes. There are observations about the uses and abuses of 
religous conversion which are not dissimilar from what we can describe in 
the current drug scene. 

In Clark's topology {W) , the outcomes can be : a sudden change of role — 
he calls this abrupt conversion. Another outcome entails an allegiance to 
values rather than a behavior change ; e.g., adolescents who are converted to 
their parents' religion. Similarly there are student LSD users who talk like 
psychedelicists but continue to be headed for a career of suburbia and the 
office. Gradual conversion entails what Clark calls role assimilation (and 
this is reminiscent of the more protracted therapies). There are clearly 
various levels of personality which can be involved either in the drug ex- 
perience or in conversion experience. Classifications of pathological outcomes 
of conversion (including irresponsibility and omniscience) startlingly re- 
semble patterns we see with LSD {20, 88). 

Even the conversion experience, if we follow Christiansen's description 
{18), is not dissimilar from that described by therapists who have worked 
with LSD. He notes a pre-conversion conflict which reaches a peak, a moment 
of "giving up" (an intention to cease the struggle) which can be followed 
by an opportunity to come up with a new solution. The conflict must 'become 
sufficiently accessible to that part of the mind which can organize and 
synthesize it in religious terms. If this did not happen there might be a 
confrontation of old intensities and strivings and continuing struggle rather 
than yielding and reworking (very much as we described in the instance 
of acting out behavior) . Such struggles in which past experience must be 
disowned yield pathologically defensive behavior, and symptoms easily ensue ; 
there would be a lack of coherence of the personality which the conversion 
experience might achieve. 



94 



LSD in Psychiatry 



There are a number of psychotherapists who have attempted to use the 
loosening of associations and the intense experiencing produced by the drug 
in order to influence behavior change. Yet the history of LSD therapy by 
physicians represents a picture of both use and abuse. In the late 1950's many 
physicians were not only struck by the drug-induced phenomena, but ap- 
parently addled by them. Perhaps they were simply jealous of the subject 
when they insisted upon taking the drug concurrently with him. They cer- 
tainly discovered a reality of the mind, but it was a region of mental activity 
about which they were supposed to be expert prior to the advent of these 
drugs. When a therapist in our culture has little sense of intellectual control 
over the events he is monitoring, we are dealing with a healing cult ; what 
is rational about therapy is our obligation to study and control that with 
which we work. Critical observation and empathy have led us as far as we 
are in our present dealing with schizophrenia ; there is no evidence that any 
further progress has been made by those therapists who insisted on being 
drugged themselves. 

There are a number of ongoing controlled projects in this country and a 
long history of experience with the use of LSD in therapy. Two major 
modes of treatment prevail. The treatment employed by many European 
workers (often called "psycholytic") represents a method by which certain 
defenses are breached. With a strong drug-enhanced tie to the therapist, feel- 
ings and memories are allowed to emerge vividly and unforgetably before 
the eye of consciousness and their strength discharged. The events are later 
worked over with care. Dosages are regulated in part by the capacity of the 
patient to steer a course between being utterly lost on the one hand or overly 
constrained by habitual defenses on the other. A kind of active participation 
in the presence of a general loosening is sought. The need for a certain 
autonomy and directiveness, a certain inner capacity to integrate and pull 
together at least a part of the experience is recognized. The integration 
which follows is a collaborative venture requiring the active participation 
and the output of the patient {2) . Yet how to reinforce any shifts in attitude 
which occur with the drug without running the risk of often repeated drug 
sessions is a largely unstudied issue. 

In the so-called psychedelic therapies as they are now being tested, there is 
an awareness of an immense amount of preparation, of salesmanship with an 
evangelical tone in which the patient is confronted with hope and positive 
displays of it, before he has his one great experience with very high doses of 
drug. The experience is structured by music and by confident good feelings. 
With the support of the positive therapist throughout this experience, the 
patient is encouraged to see his life in a new light, to think of his future 
accordingly. There now tends to be a rather long period of follow-up and 
support before the patient is discharged. An earlier mode of intervention 
attempted to avoid the tangled problems of relationship between therapist 
and patient with one single high dose drug session as the chief therapeutic 
contact; the current approach is more explicitly ritualized (in the model 



95 



of nativistic movements) , and the person and attitude of the therapist tends 
not to be analyzed but incorporated. It is speculated that the egocentric 
problems of the alcoholic may be specifically tailored for this ego- dissolving, 
ego-building teclmique. Other approaches lie somewhere between these two. 
It is interesting that peyote cultures also report cures of alcoholics, but 
the effects may not persist without sustained group support and leadership. 
The efficacy and selectivity of current therapies is far from settled and re- 
search is still ongoinsf (2) . Obviously careful follow-up is essential, since the 
immediate glow which occurs with drug-induced personality change can be 
deceptive. 

Abuse of LSD 

I have noted my current opinion that the chief abuse of LSD is irrespon- 
sible, alluring and provocative advertising. "We are surely at an advanced 
enough stage of our culture to identify- folly and even to study it. Professor 
McClelland at Harvard (44) noted some of the effects upon the research of 
the psychedelic fanatics at the height of their proselytising in the early 
1960s. He documented certain features of their research which appeared to 
be related to the drug state. Of course whether poor research is to be con- 
sidered a drug abuse is a moot point, but some of the features noted were a 
high opinion of their own proftmdity ; dissociation and detaclmient — a feel- 
ing of being above and beyond the normal world of social reality; inter- 
personal insensitivity ; omniscience and philosophical naivete — a simplistic 
satisfaction in visions. Finally he noted inipulsivity which might be seen as 
intolerance of any limits, questions or skepticism, let alone inability to predict 
the consequences of irresponsible, provocative actions. These consequences 
of drug taking observed in the very home of transcendentalism have been 
observed in other settings ; perhaps we are delineating one mtrinsic pattern 
of outcome of extensive, repeated LSD use. TVliile such descriptions may give 
us a guide for future research, conclusive and analytical studies simply are 
not available. 

In a few current illicit self-help groups the drugs surprisingly are used 
reportedly to achieve a conventional outcome. A group of ex-convicts — 
allegedly — require that members have an honest job before becoming part 
of the LSD-taking religious group. Sunilarly one group of homosexuals are 
reported to use illicit LSD to enliance heterosexual behavior. Several groups, 
recognizing that overly frequent use might have insidious and profound 
effects on judgment and that careless use can lead to dangerous panic, have 
set up agencies to be phoned when reqixired. "We seem to be living in an era 
when many practices (half-way houses, group therapies, ''cathartic" therapy) 
built into the fabric of psychiatric work are imitated by self-help groups. If 
these lay LSD groups leam from experience, they will do so with even less 
guidance and self critical checks than the professionals have had in coping 
with adolescent confusion and turmoil and even the more serious dysfimc- 
tions. It is the patient who pays for such experimentation by the gurus. On 
the other hand, other organizations such as Alcoholics Anonymous have 



96 



continued to evolve patterns of response to the problems with which they 
are concerned without damage to their adherents; members are free to get 
whatever professional help they need. The discipline of abstention and the 
general reality orientation of this group is important. 

From the evidence available, it appears that users who end up in hospitals 
with prolonged and serious psychoses are initially a quite unstable group. 
They are, in any event, a small group. More frequently one sees a transient 
panic occurring during the drug state, from which recovery is generally 
rapid. Others who have come to the attention of physicians do not require 
hospitalization but often seek treatment because they are nervous or con- 
cerned about having taken the drug, or about some of their thoughts and 
experiences during the drug state. And a few others as noted may have 
non-drug induced panics some weeks after the drug state very much as a 
bad dream recurs. It is somewhat easier within a college population to get 
some gauge on the prior adjustment of the students. Certainly there are a 
group of students, even some of the repeaters, who appear relatively stable 
{9,51,65,71,7^,75). 

Motives for Use 

The motives for LSD use are varied. Sociologists refer to problems of 
commitment and alienation and at least add thereby to the younger genera- 
tion's verbal mythology. A "need to feel" — to gain access to themselves and 
others — a pervasive sense of being constricted, seems to characterize some 
of the college takers I have studied. In a recent report {9) of a group in 
which Rorschach and other studies were available, this theme dominated 
even though outcomes sharply differed: these ranged from psychosis, to 
instability, to a reaction of bemused enlightenment. Some college students 
clearly tried the drug as a part of clique activity ; thanks in part to sustained 
advertising, drugs and drug talk are a part of a student's vocabulary. 
Taking the drug puts the student one-up — he has "been there". This is a 
challenge evoking interest among friends and can provide the basis for a 
loose group cohesion. Others sincerely feel they should confront an expe- 
rience advertised to be so important. They see the drug as an emotional 
fitness test, somewhat analogous to physical fitness. The issue for many is 
"control". They experiment with the right to drink and test their ability 
to stop. At this age they are doing the same, often, with cigarette smoking 
or with masturbation. In general they are rehearsing their strength and 
autonomy at a time when their lives are largely unwritten. Many behaviors 
of this age constitute a probing for consequences — an attempt to come to 
grips with life and to seize the fruits and risks promised in the future, the 
threshold of which is now visible. This underlies many of the grimmer 
statistics of the 18-25 age group, including accidents and suicide. One won- 
ders if these represent the inevitable costs of learning the lesson of conse- 
quences, of limits, of mortality. 



97 



Summary View of the Value of Psychedelic Drugs 



In psychiatry we know something about how to use drugs to cope with 
grossly inadequate functioning and to ^compensate for deficit states. "With 
respect to the LSD experience, we know that many serious persons have 
reported some transient or even long-term value in it. They say their aesthetic 
appreciation is enhanced, and McGlothlin indeed has some evidence for a 
slight shift of this sort in some but not all of a group of normal subjects {70) . 
If though, we search for major productions of art, letters, music or visionary 
insight, few clear cut monuments to the drug are available. Related to cre- 
ativity, the effects of the drug do not seem to have compelled it. Huxley's 
greatest output preceded his mescaline states ; he thereafter, as I read him, 
tended to write about drugs, not to create with them. If we ask whether there 
have been cultures which have eradicated mental disorders and disease with 
these drugs, or groups which have seen the dissolution of deviant behavior or 
even deviant drug-linked behaviors (for example, alcoholism), we find some 
slight association but no clear cut overall differences that I know of in the 
general titre of human misery. In fact the use of these drugs is often associ- 
ated with some form of psychosocial deprivation — or (equally) with marked 
privilege (as in Brahmins and college students). That private satisfactions 
might have been achieved, that groups with the presence of these plants could 
have attained some spiritual equilibrium seems apparent, but whether the 
plants and their effects are both necessary and sufficient to get such results — 
whether no alternative means exist within a culture — is another question. 

We should not forget to assess the cost of sustained euphoria or pleasure 
states ; we have to wonder whether the mind of man is built to accommodate 
an excess either of pleasure or of over- rationality. We do not know whether or 
not there are individuals with sufficient strength to take these drugs for 
growth or pleasure within the social order without enhanced and credulous 
alienation from it. Is a stable person really under sufficient control of his mo- 
tives and shifting circumstance, let alone the dosage, to take these drugs as a 
civil right for whatever personal reasons he wishes ? If so, who has to care for 
the consequences of his misjudgments? Some side effects cannot be avoided 
if we are correct about the way the mind is built, and if we learn from the 
effects of drugs on much simpler biological systems. How can the stability of 
religious custom protect drug takers who have little authentic orientation to 
religion and unstable groups and barely reliable leaders upon whom to lean ? 

Thus etched upon the variabilities of culture and personality are drugs 
with a certain skew toward that mystical realm of the mind which knows both 
psychosis and religion, both heightened and useful self insight, and impaired 
and distorted judgment about the everyday world. Perhaps similarities and 
differences of these various plants and their effects could — if analyzed — reveal 
means for finer control of these experiences — at least in terms of their inten- 
sities. Some research should point towards elucidation of critical neurochem- 
ical mechanisms. 

In general, it seems to me that we have been more awed than aided by our 
experience with these drugs. They still remain agents which reveal but do not 



98 



chart the mental regions; to do that we must employ our mental faculties 
available in the undrugged state. Accordingly we should do better than repeat 
the ontogeny of past encounters with mind revealing drugs. We should strive 
to make distinctions so that — at some future date — if we knew how the ele- 
ments of mind really were related, we could specify for the chemist the 
designs he should seek in nature. But to begin with we have to learn to analyze 
how behavior is organized, and to see what nature can teach us about the ways 
in which the chemical organization of the brain is related to the dimensions of 
mind. 

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99 



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102 



SESSION II 



PIPER METHYSTICUM (KAVA) 

Georg E. Cronheim, Chairman 



Chairman's Introduction 



Georg E. Cronheim 

Riker Laboratories, Northbridge, California 

The first session of this conference dealing with a particular plant, is 
devoted to Kawa or Kava-Kava or Piper methysticum, which is indigenous 
to many islands of the South Pacific. 

The use of Kawa in certain parts of Oceania is apparently very old. It 
has been described already by early travelers, for instance by James Cook 
in 1768. It is important to remember that the Kawa drink is mentioned not 
only quite early, but also repeatedly by a number of observers. The descrip- 
tions uniformly indicated that the Kawa experience is apparently pleasant, 
and free from hangover or other side- or aftei'-effects. Many travelers, and 
also such scientific investigators as L. Lewin, have reported that Kawa can 
induce a form of euphoria, described as a happy state of complete comfort 
and peace, with ease of conversation and increased perceptivity, followed 
by restful sleep. 

In many areas, the use of Kawa was connected with religious cults and 
ceremonies. Thus, it is not surprising that missionaries tried to suppress the 
drinking of Kawa. In some islands, this campaign was very successful, 
especially when it coincided with the introduction of alcoholic beverages. 
This replacement of Kawa by alcohol may have some significance, which I 
hope will be discussed by some of the speakers. Could it be that enough 
people preferred the effects induced by alcohol over those of Kawa ? Other- 
wise the change-over would not have taken place as rapidly or as completely 
as was apparently the case in many islands. Also, the preference for alcoholic 
beverages is — if not an absolute proof — at least a good indication that the 
Kawa drink did not contain or simulate alcohol. 

The first major scientific examination of Kawa was published by L. Lewin 
in 1886. Subsequently, other investigators in Europe and in this country 
studied the chemical constituents and the pharmacological properties of 
Kawa and of its components. However, the number of people interested in 
this plant was always relatively small. Kawa did not become the subject of 
more wide-spread use (or mis-use), or of numerous scientific investigations. 
Perhaps our colleagues in anthropology and sociology can tell us whether 
this is purely coincidental or whether there is some specific reason that in 
spite of the sudden interest and cult-like fadism related to substances with 
hallucinogenic or euphoria-producing properties, Kawa remained, outside 
of the South Pacific Islands, a relatively little known drug. Moreover, the 
fact that Kawa did not gain any popularity may have another explanation. 
In more recent references to the Kawa Ceremony and present-day Kawa 
use, none of the previously described effects on the central nervous system 
were mentioned. This represented always a great puzzle. How could one 
explain numerous detailed eye-witness accounts of unmistakable central 



262-016 0-67— 9 



105 



effects of Kawa when taken by natives or by white people, travelers or 
settlers? Even addiction has been described for these groups. Also, Kawa 
was an article of commerce. Still more important, it was not just collected 
as a wild plant, but was regularly cultivated. In other words, Kawa repre- 
sented something which native people in the South Pacific Islands wanted 
and for which they were willing to pay in the form of money or physical 
labor. Doesn't it seem reasonable to assume that they derived some pleasure 
from Kawa? And wouldn't tliis explain that drinking of Kawa — both for 
ceremonial and social purposes — is still practiced? 

Pharmacological studies of Kawa and certain of its constituents have 
shown some rather remarkable properties, which will be discussed in the 
course of this program. Studies in our laboratories were in fact so promising 
that we carried out the necessary chronic toxicity studies in animals, in 
order to permit an evaluation in human volunteers and in patients. Unfor- 
tunately, the results were not very striking. Some anti-epileptic activity was 
seen in patients, but none of the "tranquilizing" effects that had been 
described. At the same time, signs of skin reactions became apparent, which 
precluded further chronic administration. 

So here we have some obvious discrepancies, for which I am sure there 
must be some explanation. It is the purpose of the present conference to 
present such discrepancies and questions to groups composed of anthro- 
pologists, botanists, chemists, clinicians and pharmacologists, because the 
complementary approach evolving from an interdisciplinary discussion has 
the best chance of solving some of the existing problems. 

We are fortunate that the group of speakers in this Kawa symposium 
includes three investigators who have had extensive first-hand knowledge 
of the use of Kawa in various island groups of the South Pacific. This infor- 
mation will be supplemented by some clinical observations in patients, as 
well as special investigations of central nervous system effects of Kawa and 
some of its constituents in human volunteers. The pharmacological proper- 
ties of these substances and the chemistry of Kawa will also be presented 
in adequate detail. All in all, a fairly comprehensive picture of Kawa should 
emerge. It is my hope that the combined knowledge of the seven speakers, 
each a specialist in his field, may provide some of the missing answers to 
the Kawa problem. 



106 



The Function of Kava in 
Modern Samoan Culture 

Lowell D. Holmes 

Department of Anthropology, Wichita State University, Wichita, Kansas 

In the Manu'a island group of American Samoa no formal or informal 
meeting of chiefs would be complete without the distribution of the tradi- 
tional Polynesian beverage kava. This drink known locally as ''ava, is pre- 
pared by steeping the pulverized roots of the Piper methysticum plant in a 
prescribed amount of water until a cloudy, khaki-colored liquid is produced. 

Kava is in no way alcoholic, but much has been made of its narcotic prop- 
erties. Early missionaries maintained that the concoction partially paralyzed 
the lower extremities, making it difficult to walk. More recent partakers of 
kava, including the author, have experienced no debilitating effect which 
could be attributed to consumption of the drink. Instead they have found it 
a refreshing, astringent drink which produces nothing more than a tingling 
sensation in the mucous membrane of the mouth and a short-lived numbness 
of the tongue. The partial paralysis of the lower limbs is not caused by the 
kava but by sitting cross-legged for hours while the kava ceremony is in 
process. Samoans who find the sitting posture a more natural one do not com- 
plain of any impairment to walking. Missionary V. A. Barradale, writing in 
1907 stated, "I have heard it said that if people drink too much [kava], it 
makes them drunk in their legs; it paralyzes their lower limbs, and they 
have to sit where they are till the effect wears off. But it would certainly need 
a very large quantity to affect a man in that way, and I never saw or heard of 
any one in that condition" (^). 

Although Beaglehole {3) reports rare cases of kava addiction in Pangai, 
Tonga, such a phenomenon was not personally observed in Samoa. The 
author's informants did on one occasion refer to one recently deceased chief 
whom they believed drank kava in excess because he had it prepared every 
morning so that he could partake throughout the day. They also felt this 
excessive use of kava was the cause of his death. Actually he had died at the 
age of seventy-five from cancer of the stomach. Another claim made by native 
informants is that over-indulgence of the drink can result in skin diseases 
and eye ailments. The literature produced by early missionaries contains 
numerous references to a scaly skin condition being attributable to kava 
drinking. These claims were not corroborated by the author. One European 
observer believed that the consumption of kava had the effect of preventing 
the Samoans from developing a taste for alcoholic liquors. The author has 
not observed this phenomenon either. 

Kramer reports that he observed the addition of Capsicum pepper pods to 
the kava concoction and believes this strengthened its stimulating effect 
thereby rendering kava the equivalent in its use to Piper hetle in Indonesia. 



107 



He tells of having broken open a Gapsicwn pod and accidentally having 
touched his face with his soiled hands. He complains of having "endured 
severe pain for a long time; thus the pepper affects even the epidermis." {6). 

The addition of this pepper to the kava mixture was not observed in con- 
temporary Samoa, and the extent of its use in earlier days is not known. 
Kramer is the only 19th century observed to record its use. 

Kava is often drunk by Europeans, who upon acquiring the taste, find it 
very refreshing. Many urban centers in the South Seas boast kava saloons 
where local businessmen— native and European — take a kava break during 
the mid-morning hours. Some government offices have kava prepared in the 
morning for the comfort and enjoyment of their employees. 

The relative importance of kava varies from island group to island group. 
Kava drinking in Polynesia is primarily a phenomenon of the cultures in the 
west, such as Tonga, Fiji and Samoa. The plant does not grow on the atolls of 
the Tokelaus. Beaglehole {3) reports universal use of the beverage in Tonga, 
but maintains that accompanying ritual is almost totally absent in villages 
inhabited by commoners. Hawaii and Tahiti had the drink at one time but it 
has practically disappeared in recent years. The Cook Island cultures for- 
merly used the plant for drinking purposes also, but many of the Bernice P. 
Bishop Museum monographs on the cultures of this region do not even men- 
tion kava. The Maori did not drink kava although a variety of the plant which 
could have been used for such purposes was indigenous to New Zealand. 
Aitken {1) reports that in the Australs the occasional and somewhat unim- 
portant practice of kava drinking was abolished by missionaries in 1822. New 
Caledonian Polynesian populations are described by Leenhardt (7) as ignor- 
ing the plant altogether. 

Other centers of kava drinking in Oceania are Ponape in the Carolines, 
the Marind District of West New Gruinea, the New Hebrides and the Wallis 
and Futuna islands. In Melanesia the drink is described as being made from 
fresh roots, and the concoction is said to have the effect of rapidly inducing 
deep sleep. Chronic drinkers in this area are said to suffer from a state of 
depression accompanied by a permanent decrease in appetite. Malnutrition 
is also said to be observed among some addicts. The difference in effect be- 
tween this area and western Polynesia is possibly attributable to the state of 
the kava root at the time of production of the beverage. The dried roots used 
in Polynesia apparently do not produce as strong a drink as that concocted 
from fresh ones. 

In Samoa it appears that kava drinking and its attendant ceremonies has 
a long history, the practice being intimately related to indigenous religious 
practices and village social and political organization. Mythology relates how 
kava drinking was given to mortals by the first high chief, Tagaloa Ui, and 
prescribes the form for modern kava ceremonies. The myth which provides 
these sanctions was recorded in Manu'a as follows : 

Not far from the village of Fitiuta there is a place where the rising sun is first seen 
in Samoa. Tliis place is called Sana. Long ago there was a custom that one day a year 
one of the families of Fitiuta must sacrifice the daughter to the sun. On the day of the 
"celebration of the sun" a daughter from the family of Matainaumati went to Samoa 



108 



to be sacrificed. The girl's name was Ui. When the sun came for the girl he saw that she 
was very beautiful and instead of eating her he decided to take her as his wife. He 
took the girl to live with him in the sky. After a time she became pregnant and wanted 
to go home so that her first child could be born in her family's village, and she wanted 
to show her parents that she had not been killed. 

While journeying home, Ui had a miscarriage, and the fetus floated away upon the 
waters where it was found by the hermit crab, (he plover and the shrike. By manipulating 
the fetus and breathing life into it the animals created the first Samoan chief, Tagaloa Ui. 

After his creation Tagaloa Ui made a kilt for himself out of ti leaves and started to 
walk toward the village of Fitiuta. On his way he walked through a grove of kava 
plants and discovered the house of the mortal, Pava. Pava invited the chief to enter his 
house and there the first kava ceremony involving mortal men was held. 

When Tagaloa Ui entered the house he took a place at the end of the house (today the 
seat of honor), and Pava sat in the front of the house (the traditional place for talking 
chiefs) and began to prepare the kava. Pava chewed and spit the kava into a taro leaf 
(laupula'a) which served as the kava bowl. Cups consisted of tautava leaves, and Pava 
used his fingers to wring the kava as no strainer was then known. 

While Pava'was wringing the kava, his son, Fa'alafi, laughed and played near the 
bowl. Tagaloa Ui instructed Pava to make the boy sit down and be quiet, but nothing 
was done about the irreverent boy. After several unheeded warnings, Tagaloa Ui picked 
up a coconut frond, formed it into a knife, and cut Pava's son into two pieces. Then 
Tagaloa Ui said to Pava, "This is the food for the kava. This is your part and this is 
mine." Pava mourned and could not drink the kava. 

Then Tagaloa Ui said, "Let us have a new kava ceremony." The kava and the leaf 
bowl and cups were thrown away and Tagaloa Ui told two of Pava's sons to go to the 
highest mountain, the house of Tagaloa Lagi, and bring down a wooden kava bowl, coco- 
nut cups, a hibiscus strainer and a new kind of kava, latasi, a single branch kava tree. 
These things were brought, and a second kava ceremony was started. Again Pava served 
as the kava wringer, and when the kava was ready, Tagaloa Ui said, "Bring me my cup 
first." Tagaloa Ui did not drink the kava but poured it onto his piece of the dead son 
of Pava and then onto Pava's piece. Then he said, "Soifua" (life). The two parts came 
together and the boy lived. Pava was so happy he clapped his hands. Pava drank his 
cup of kava and Tagaloa Ui gave the following orders : "Pava, do not let children stand 
and talk while kava is being prepared for high chiefs, for the things belonging to the 
high chiefs are sacred." 

A number of ritual details of the modem Samoan kava ceremony seem to 
relate directly to this myth. They are: 

1. The seating arrangement of the chiefs and the talking chiefs. 

2. Prohibitions against children, or indeed any unauthorized untitled 
persons, attending the ceremony. 

3. The solemn atmosphere which must prevail. 

4. The proper equipment for the production and distribution of kava — 
a carved wooden kava bowl, a hibiscus strainer, a coconut cup, and 
a certain type of kava. 

5. The order of drinking — high chiefs first, talking chiefs second. 

6. The pouring of a bit of kava from the cup onto the mat. 

7. The concept of food for the kava. 

8. The use of the term '■^Soifica." 

9. The clapping of hands when the kava is ready. 

10. The duty of talking chiefs to direct the kava ceremony. 
The importance of the above is indicated by the fact that although short- 
cuts are often taken in the modem kava ceremony the features listed are 
seldom if ever altered. 



109 



Kava in contemporary Samoan society has been likened by Keesing (5) to 
the European cocktail or highball, in that it produces a relaxed and friendly 
atmosphere conducive to social cooperation. 

Every chief is expected to keep a stock of dried kava on hand for his own 
use and for the many demands made upon him by the protocol of hospitality. 
Whenever any elite visitor enters the village, the welcoming ceremony re- 
quires that each of the host chiefs present him with a dried kava root. 

The kava ceremony is invariably the initial act of any meeting of the vil- 
lage council (/(mo) , and is therefore a definite part of formal discussion and 
decision making. It is also an essential part of all ceremonies associated with 
births, marriages, deaths and title installations. No bonito canoe or house is 
ever constructed without the labor being prefaced by the kava ceremony 
wherein the carpenter is served first kava in the name of Sao (a name which 
people claim was given to the first carpenter by the god Tagaloa) . The cere- 
mony is said to insure successful work. 

Kava drinking is without doubt the most important element of the aiavd, 
the ceremony of greeting for visiting parties (m-alaga), and therefore carries 
much of the biirden of Samoan hospitality. 

In earlier, less peaceful days kava was consumed by warriors prior to battle. 
On such occasions, the ceremony was referred to as ^ava mua au. Fe'epulea'i 
Eipley (7) reported observing such a ceremony wherein the chiefs lined up 
along each side of the road and set up the kava bowl in the middle of it. 

Aside from its ceremonial use, kava is reported to have certain medicinal 
uses. It is often consumed in an attempt to counteract the chills which ac- 
ompany filariasis. Some Samoans believe that kava chewed in large quantities 
will cause abortion. It is also claimed to be a cure for gonorrhea, and it is a 
matter of record that German drug houses at one time imported small quan- 
tities of the plant for this purpose. 

Although the kava ceremony is considered the exclusive property of titled 
men there are certain ceremonial occasions, such as the entertainment of a 
visiting party, when the society of imtitled men (atomagra) or the wives of the 
village chiefs (Woman's Committee) conduct their own social kava ritual. 
On such occasions the order of drinking is determined by one's relationship 
to the title holders of the village. Having a father or husband who is the vil- 
lage paramount chief entitles one to be honored with first kava. 

Some regional variations in kava rituai may be observed from village to 
village, and even in a given village the ceremony is not always performed in 
the same way. Certain parts may be abbreviated or eliminated altogether, and 
perhaps the ceremony to be described in this paper is closer to the ideal than 
to the real. However, all the steps described herein have been observed fre- 
quently on occasions of high ceremony. Regional variations include differ- 
ences in who may wring kava, the number of attendants involved in serving 
the kava, and in some cases, the status and sex of those served. In some villages 
only men are permitted to wring kava, but in others the ceremonial village 
maiden (faupou) may do the honors. On the island of Tutuila it is not un- 
common for women to hold matai titles and serve on the village council. They 
are, therefore, as titled individuals, qualified to participate in the kava cere- 



110 



mony. In Manu'a women neither hold matai titles nor partake in the drinking 
of kava at formal ceremonies where chiefs are present. The one exception to 
this was the female sovereign Tuimanu'a Makelita. 

The Modern Kava Ceremony 

In preparing for the modern Manu'an kava ceremony the talking chief who 
will later direct the kava distribution selects a piece of kava root. This part 
of the kava plant is called the Brother Roots {''ava uso). The name drives 
from a rajth. which recounts how two brothers, the sons of Tagaloa, found a 
piece of floating wood while swimming west from the Manu'a Group. They 
divided the wood and used the two pieces as floats. One of the brothers re- 
turned to Fitiuta where many similar plants were observed to be growing 
already, while the other brother swam on to Western Samoa where kava was 
unknown. Here he planted his piece of wood and thereby introduced kava 
drinking in this area. 

After the initial selection of a piece of kava root, the society of untitled men 
{amnaga) takes over and the root is cut into still smaller pieces by one of 
their members. In this form kava is known as una o le V a sd, scales of the 
sacred or forbidden fish. This term alludes the fact that like many other sacred 
or taboo foods kava is reserved for the exclusive use of the chiefs. 

Wliile the pieces of kava were formerly chewed, final processing today 
involves pulverizing in a crude stone mortar (■tna'a tu''i''ava) . Other prepara- 
tions for the ceremony include washing the kava bowl and bringing water in 
coconut shell containers (sometimes a galvanized bucket is substituted today) . 

A full inventory of the ceremonial paraphernalia includes a carved bowl, 
eighteen inches in diameter, which traditionally had four legs but now may 
have as many as twenty-four, a strainer made of shredded hibiscus bast, and 
a polished coconut cup. 

Village kava ceremonies are usually held in the house which serves as the 
meeting place of the village council. As the chiefs enter the council house an 
attitude of reverence prevails. Nothing may be worn above the waist, and body 
ornaments of all types must be laid aside. The men speak in whispers and 
refrain from smoking as the kava ceremony begins. 

At a place near the back of the house three untitled men, members of the 
village avmaga, station themselves at the kava bowl while a fourth remains 
outside to clean the hibiscus strainer of kava fibers when it is periodically 
thrown to him by the wringer. The man who is to wring the kava sits im- 
mediately behind the bowl with a water pourer to his right, and to his left, 
the man who will carry the cups of liquid to the assembled chiefs. Several 
taboos must be observed by the wringer. These include never wearing a 
flower necklace, a ring, a shirt or any other clothing except a wrap-aroimd 
{lavalava) . Lavalavas of all untitled men involved in the ceremony must be 
worn so they do not extend below the knees. The wringing of the kava must 
be done correctly and with precision. Untitled men take pride in their ability 



111 



in tHs art. There are a nxunber of specific steps in the preparation of the 
liquid, and each has a traditional name. They are : 

1. Fa'apidcfu — Covering the kava in the bottom of the bowl with the 
strainer. 

2. Vau — Pressing down on the strainer with the heels of the hands and 
with the fingers. 

3. Aoga — (Collecting pieces of kava fiber in the strainer by drawing 
it toward the back of the bowl. 

4. Tatau — ^Wringing the kava. The strainer is lifted from the bowl and 
wrung three times only. It is grasped in both hands like one would 
grip a baseball bat. At the end of each wringing stroke the clenched 
hands are bent forward so the liquid will not run down the arms. 

5. Mapd — Cleaning the strainer. After the above steps have been car- 
ried out three times the strainer is passed under the right knee of the 
wringer and thrown back, with a side arm motion, to the untitled 
person outside the house who catches it in his right hand and removes 
the kava particles in it by snapping it three or four times. The 
hibiscus strainer is then thrown back underhand and caught by the 
wringer in his right hand. 

The above process is continued until the bowl is free of pieces of kava root. 
When this has been accomplished and the kava is ready for drinking, the 
wringer wipes the rim of the bowl, cleans the strainer himself by snapping, 
forms it into a ball, and plunges it into the kava, and lifts it above the 
bowl with both hands, allowing the stream of liquid to fall into the bowl. 
This final gesture, known as sila alofi, permits the chiefs to see whether the 
kava requires more water. It is said that the correct mixture is judged by 
the sound of the kava splashing into the bowl as well as by its color. 

If the talking chief serving as kava announcer does not call for more 
water the liibiscus strainer is wrung out and placed on the rim of the bowl. 
The kava wringer then places his hands on the sides of the bowl, liis right 
covering the strainer. He remains in that position until the kava has been 
distributed. 

It is the responsibility of the talking chief directing the ceremony to 
watch the progress of the wringing from his position behind and to the right 
of the bowl. Wlien the kava is nearly clear of fiber particles, he must com- 
mence the verbal part of the ceremony with a poetic recitation (solo) 
which recounts the mythical origin of the kava or particular kava cere- 
monies of importance held by the ancient Samoan gods. A typical solo is as 
follows : 

Si'i le f aiva e to'alua 

Papa ma Lotulotua 

Aumai se i'a setasi 

Le Manini mai le Sami 

Telemu ma Telea'i 

O mai lua te tauf etuli ile lagi 

Fati mai se la tasi 

Se la o le la 'avao tu felata' i 



112 



Gaugau ma sasa 
Gaugau ma f alava 

Translation 
Two people went fishing 

Papa and Lotulotua (members of the Tagaloa family) 
They brought one fish 
The Manini, from the sea. 

Telemu and Telea'i (two brothers of the Tagaloa family) 
Were sent to run to the heaven 
To bring a branch of kava 
They broke and hit the kava 
They broke and hit the fierce kava 

Many solos are traditional, but clever talking chiefs may and do compose 
their own. It will be noted that the example given above is composed of 
rhyming couplets. There is, however, little concern for rhythm. The solo is 
timed to be finished the moment the kava is completely clear of fibers, 
whereupon the kava announcer states, "Z7a usi le aloft'''' (The kava is already 
cleaned). The color and consistency of the mixture is then analyzed and if 
pronounced acceptable, the assembled chiefs respond by clapping their hands 
several times. Informants state that this act of clapping corresponds to the 
clapping of Pava when his sons was returned to life through the action of 
Tagaloa Ui at the first kava ceremony. 

The distribution of kava begins by calling the cup title of the high chieJ 
who, because of his rank, is permitted to drink first. It must be understood 
that the cup title is not the family title of the chief. For example, in Si'uf aga 
village High Chief Lefiti (Lefiti is the family title) has the cup title 
Lupe lele talitali lau ipu (The pigeon who flies, receive your cup). Only 
high chiefs have cup titles. Talking chiefs receive their cup after the an- 
nouncement of their family title and the words "Zaw ^ava'^ (your kava). 
Chiefs of secondary rank receive the cup after their family title and the 
yvord'^^ Taumafa'^ (drink) is pronounced. 

The order of drinking is of the utmost importance as it signifies the rela- 
tive rank of the drinker. The chief of highest rank in the village receives 
first kava; the highest talking chief, second; second highest chief, third; 
second highest talking chief, fourth; and so on down the ranks of chiefs 
and talking chiefs. In some villages this procedure is altered, and certain 
divisions of chiefs, or certain sections of the village, drink before others. 
To drink last kava is as prestigef ul as to drink first. 

Drinking etiquette, which varies according to rank, is as follows: When 
the high chief receives the cup he does so with both hands. Before drinking 
he pours a few drops onto the floor mat and says, "/a fa'atasi le Atua ma i 
tatou i lenei aso^'' (May God be with us today) or '•'•la taHtaH le Atua i lenei 
aso''' (May God be our leader for today) . Smith {8) records a typical prayer 
as, "Let the god drink kava that this gathering may be pleasant." 



113 



Following this prayer the high chief raises his cup, says "Soifna'^ or 
'■^Manuia,^'' and drinks what is contained in the cup. If the high chief says 
'■^Soifua''^ the other chiefs respond with ^^Manuia.^^ If the latter word is 
pronounced by the drinker the chiefs reply with '■'■Soifiiu.'''' Informants point 
out the connection between this aspect of the modern kava ceremony and 
the action of Tagaloa Ui in the first kava ceremony. The pouring of kava 
onto the mat represents the pouring of the liquid onto the two parts of the 
dead son of Pava, and the word "xS'o^/m," which may be translated "Life" or 
"May you live," alludes to the command given by Tagaloa Ui when he 
performed the miracle of returning the boy to life. The word '"''Manuia^'' 
may be translated "Blessings" or "May the gods bless you," and perhaps 
relates to an expression of gratitude by Pava. It is also contended by in- 
formants that the right of the high chief to drink first kava and to sit in 
the end of the house is sanctioned by the Tagaloa Ui myth. 

The drinking etiquette to be observed by a high talking chief varies some - 
what in that he receives the kava cup with two hands if high chiefs are oc- 
cupying both ends of the house, but if only one high chief is seated to the 
high talking chief's right, the cup must be received with the left hand to 
avoid showing the high chief the back of the hand. Of course the cup will be 
taken with the right hand if the high chief is seated to the talking chief's 
left. A high talking chief usually does not pour any kava onto the floor 
mat although he may say "Soifua" or "Manuia" before drinking. 

Chiefs and talking chiefs of secondary rank do not pour kava onto the 
mat, nor do they say anything before drinking. Furthermore, they are not 
expected to respect the position of the high chief by receiving the cup with 
any particular hand. 

Some Samoans do not care for kava and they "drink" symbolically by 
merely touching the bottom of the cup as it is passed to them. The cup 
may also be raised in a form of salutation and then returned to the cup 
bearer, with the kava untouched. On rare occasions a chief may take the 
liquid into his mouth, swish it about and then turn and spit it out onto the 
apron of the house outside. All these actions represent acceptable etiquette for 
the non-drinker. 

When many chiefs are assembled there is often not enough kava to serve 
everyone. In such cases it is important for the kava announcer to judge when 
but a single cup of kava remains and then to announce rapidly the names 
of those who are entitled to drink. Following the recitation of this list of 
titles the announcer calls the cup title of the high chief who is then honored 
by drinking last kava, and the final cup is served to him. When talking chiefs 
of secondary rank are aware that there is not sufficient kava to go around 
they will often interrupt the announcer and call, "I will drink with my chief." 
When this occurs the lesser talking chief's title is not announced but the cup 
is taken to him immediately after the high chief of his family has been 
served. 

Partially consumed kava must be cast away and the cup returned empty. 
It may be handed or thrown back to the server. If the cup is thrown to the 
server it is done to test his alertness. 



114 




Front 



1 = Serving route to paramount high chief (PC); 2 = Serving route to high chief (HC) 
3 = Serving route to talking chiefs (TC); 4 = Serving route to lesser chiefs and talking 
chiefs (LC) ; 5= Serving route to high chief who will receive last kava (HC) ; + = Point 
at which the kava server stops before approaching chiefs of high rank. 

All aumaga members who expect to take part in the kava ceremonies must 
master the etiquette of serving kava. Each rank of chief or talking chief must 
be served in a special and distinct manner. Respect is paid to the half of the 
house in which the paramount chief is seated, and the kava server must 
walk in this area as little as possible in making his rounds to the drinkers. 

When serving a high chief the kava distributor dips the coconut cup into 
the kava and carries it with the thumbs and index fingers at the level of his 
waist to the center of the house where he stops, raises it to his forehead and 
walks in the direction of the high chief. About four feet from the chief, 
the server lowers his right hand and with his left, places the cup on his 
upturned right palm. The left hand is placed behind the back, and the cup 
is handed to the high chief chest high. The young man then walks to the 



115 



center of the house where he stands at attention until the chief has finished 
drinking. 

Lower ranking chiefs are served kava with the right hand, but in the 
case of these lesser personages the cup is held by the edge with the thumb in- 
side, thus showing the palm of the hand to the chiefs as it is presented to 
them. 

In serving a high talking chief, the cup is held by the edge with the thumb, 
index and middle finger of the right hand. As it is carried from the bowl 
it is held just above the left shoulder. When in front of the high talking 
chief, the kava server swings the cup forward and down, presenting it with 
the back of his hand toward the talking chief. The kava cup for lower 
ranking talking chiefs is carried in the right hand, waist high, but is 
presented with the left. As in the case of high talking chiefs, the cup is 
held by the edge and the back of the hand is shown to the drinker. 

After delivering the kava the server returns to the center post of the 
house and stands facing front while the kava is consumed. In rare cases he 
may return to a position in front of the kava bowl and face the front 
of the house. 

When all of the assembled chiefs and talking chiefs have drunk or 
have been acknowledged as having the right to drink, the kava announcer 
concludes the ceremony with "Z7a moto le alofi''' (The kava is finished). 
'•'•Ale le fau ma le ipu e tautau''^ (The bowl will hang with the fau (strainer) 
and the cup). Perhaps a more traditional closing is that recorded by 
Smith (9) as "Ze ^ava ^au motv}'' (The kava is broken off). "Z7a matefa le 
fau^^ (The strainer is poor). "Z7a pa'u le aloP'' (The company of chiefs 
has fallen down). 

The assembled chiefs respond to these final words of the kava announcer 
with an expression of thanks, "maZo fa^asoasoaP At the conclusion of 
the kava drinking ceremony there is always the fono o le ''ava (food for 
the kava ceremony). According to the Tagaloa Ui myth the food for the 
first ceremony was the son of Pava and the food for the second was the 
sacred fish Manini and tcdofa'afana (recooked taro). Today the Manini 
and talofa'afana remain the traditional foods for the kava ceremony but 
there are frequent substitutions of rice, tinned beef, or other prestige 
foods. 

The present day kava ceremony contains a number of elements which 
can be traced to older religious concepts of Samoan culture. The pour- 
ing of a bit of kava onto the mat not only relates to ancient mythology, 
but a number of scholars feel that it is a ritual reenactment of an ancient 
religious custom of pouring an evening oflFering to family or village gods. 
Steubel records in Samoanische texte (1895) that the typical prayer 
accompanying this act was "O the kava to drink of thy highness Sepo. Be 
lovingly disposed. Bless this village." (Sepo was primarily a war god, but 
in many villages served as a household god. ) 

Mead {8) suggested that the casting away of unconsumed kava may be 
related to ancient ceremonies wherein kava was entreated to depart and 
take all misfortune with it. On the other hand it may be related to precau- 



116 



tions about unconsumed food or drink which might be used for purposes 
of sorcery. Certainly the sanctity of the mixing bowl and gear, the air of 
solemnity and respect which accompany the entire ceremony, and the in- 
clusion of poetic recitations which always allude to ancient Samoan gods, 
testify to the religious nature of the ancient ceremony. 

Although the kava ceremony contains these unmistakable references 
to pre-Christian religion there seems to have been no great problem in 
fitting it into the Christian context. Bits of Christian prayer frequently 
accompany the pouring of kava onto the mat prior to drinking, and it is 
not uncommon to see local pastors included in the kava circle. On such 
occasions the village pastor {faife'au) drinks first kava, thus being ac- 
corded honors even greater than those shown to the village paramount 
chief. Since village pastors do not hold titles, their privileged position of 
drinking indicates their exalted status within the social structure of the 
village. Samoan medical practitioners and village school teachers are 
accorded similar honor by being served kava second only to the highest 
village chiefs. 

Neither the church nor the American government has attempted to do 
away with the kava ceremony, and it is not unusual to see chiefs partake 
in a communion service in church, and then go home and conduct a kava 
ceremony while waiting for the midday meal. All visiting dignitaries in 
American Samoa, including President Lyndon B. Johnson in 1966, are 
honored with a kava ceremony by the paramount chiefs of the territory. 

It has been said that while other Polynesian people worshipped gods, 
Samoans worshipped their village and social organization. The kava cere- 
mony would seem to be a part of this veneration. The detailed etiquette 
of serving, the prescribed order of drinking, the use of special honorific 
cup names, and the insistence that the beverage be prepared and served 
only by specially qualified persons, have been tremendously important in 
dramatizing the whole system of Samoan rank and prestige. When the 
kava ceremony is completed there is little doubt of the status of those 
present and of the rights and privileges of their respective offices. Through 
continual ceremonial exercise, social relationships are reiterated and 
Samoan values are intensified. The result of this seems to be an unusual 
stability and resistance to change which is found among few other Poly- 
nesian peoples. In an attempt to explain this remarkable resistance to 
change, John Copp has commented, "Samoan custom now serves as a 
'refuge' from the conflict of choice and judgment resulting from Western 
contacts." {11). Perhaps it has been the stabilizing influence of the kava 
ceremony and other rituals that has allowed the Samoans to make satis- 
factory adjustments to European influences. Traditional aspects of Samoan 
culture such as the kava ceremony are, in a manner of speaking, bits of 
solid ground on which to anchor in a changing world. 

It is believed that the influence of the kava ceremony is one of the ex- 
planations for the amazing stability of a people who, as Douglas Oliver 
puts it, have survived "the strong impact of western civilization without 
losing their numbers, their strength, their dignity, or their zest for a good 
fight." (P). 



117 



BIBLIOGRAPHY 

(/) AiTKEN, Robert T. "Ethnology of Tubuai." Honolulu, Bishop Museum Bulletin 
No. 70, 1930. 

(2) Barradale, V. A. "Pearls of the Pacific." London, London Missionary Society, 1907. 

(3) Beaglehole, Ernest and Pearl. "Pangai : Village in Tonga." Wellington, Poly- 

nesian Society, Memoir Vol. 18, 1941. 

( 4 ) Buck, Sir Peter. "Samoan Material Culture." Honolulu, Bishop Museum Bulletin 

No. 75, 1930. 

(5) Keesing, Felix. "Elite Communication in Samoa." Stanford, Stanford University 

Press, 1956. 

(6) Kramer, Augustin. "Die Samoa-Inseln," Stuttgart, 1902. 

(7) Leenhardt, Maurice. "Gens de la Grande Terre." Paris, 1937. 

(8) Mead, Margaret. "Social Organization of Manua." Honolulu, Bishop Museum 

Bulletin No. 76, 1930. 

(9) Oliver, Douglas. "The Pacific Islands." Cambridge, Harvard University Press, 

1951. 

(10) Smith, S. Percy. "Kava Drinking Ceremonies among the Samoans and a Boat 

Voyage round 'Opulu Island, Samoa." Journal of Polynesian Society Supple- 
ment, 1920. 

(11) Stanner, W. E. H. "The South Seas in Transition." Sydney, Australasian Pub- 

lishing Co., 1953. 



118 



Recent Observations on the Use 
of Kava in the New Hebrides 

D. Carleton Gajdusek 

National Institute of Neurological Diseases and Blindness, N.I.H. 
Bethesda, Maryland 

Of all the Pacific islands on which kava is still used today, Tongariki is the 
one on whicji its use has attained maximum frequency and intensity. I have 
had occasion to be resident, with Professors Jean Guiart and Robert Kirk, 
on this small island of the Sandwich group in the New Hebrides, for several 
weeks in two periods during the past three years, while working on an in- 
tensive study of human adaptability in isolated populations. Quite apart 
from our medical and genetic studies, we were soon aware that the entire 
social life, mood and spirit of the island villages changed nightly at dusk to 
a more subdued, Avhispering and cautious quiet than we had seen in native 
villages elsewhere in the Pacific. This restrained atmosphere we found to be 
caused by kava drinking : nightly, most of the men Avere drinking fresh kava. 

Whereas on most Pacific islands kava prepared by the ancient technique of 
premastication (particularly of the fresh, undried root) has been abandoned 
in favor of a much less pharmacologically potent beverage made by grating 
or pounding the root, usually dried, here on Tongariki the current extensive 
nonceremonial drinking of kava makes use of the "green", freshly harvested, 
locally-grown root and of mastication and salivary digestion of the pulp by 
the adolescent and young men. Fresh cold water is used with hand mixing 
and wringing through a sieve of cocoanut fiber to extract the active in- 
gredients from the chewed pulp. The many variations of this procedure have 
been described exhaustively since the earliest reports from Captain Cook's 
voyages, and similarities in minute details of the kava ceremony have been 
used to suggest affinities between peoples on different islands. On Tongariki 
the procedures are now relatively unformalized and thus subject to consider- 
able variation. Kava drinking on this island is unusual, furthermore, in that 
its extent and pattern is a relatively recent phenomenon, and in that it has 
reached faddish proportions in terms of the number of kava drinkers and 
the frequency of their use of kava, which in both cases exceeds that of pre- 
European contact. 

This resurgence of kava drinking suggests the extensive revival of kava 
usage on the southern New Hebridean island of Tanna in the early 1940's as 
a ritual of a flourishing cargo cult which repudiated much of the missionary 
teaching. Jean Guiart, in his study of this cargo cult, believed that the fierce 
battle the Presbyterian Church had waged against kava drinking had focused 
undue attention onto the traditional use of the beverage ; this served to endow 
its new prohibition-defying use with such psychological import that the re- 
newal of kava drinking became an important part of this anti-missionary 



119 



movement, which appeared on the island during World War II and has not 
yet subsided. Early in the cargo movement (called the John Frum movement 
after a neomythical man of that name) there was an anarchical use of the 
drink, without respect for the ancient ceremonial and age-group restrictions 
on its use; even adolescents drank it; the drinking took place in small in- 
formal groups at odd times of the day and in unappointed places, as was 
never permitted in pagan times. 

Tongariki has a population of about 500 living in four small villages ; it 
has not had a full-blown cargo cult or Messianic movement, but the resur- 
gence of the use of kava has been associated with a reluctance to bojome 
involved in Protestant mission or government -instigated activities, an in- 
creased clannishness, and a withdrawal from outside contacts. No European 
missionary has ever been resident on Tongariki, but native missionaries from 
other islands have been sent there by the Presbyterian Church. In spite of 
attempts to suppress it, the use of kava here was never fully stopped; in 
recent years most adult male members of the population turn each night to 
kava. Moreover, only the fresh root and not the dry variety is usually em- 
ployed. The users still attend Sunday church services on the island, and do 
not associate their use of kava with a revolt against the church such as 
occurred on Tanna. 

Kava drinking on Tongariki is a relatively relaxed and unceremonious 
affair, without the strict adherence to prescribed etiquette characteristic of 
kava drinking in much of the Pacific. It is prepared entirely by chewing, 
never by the use of mortars, graters, or other mechanical aids. Boys from 
pre-adolescent age to young adulthood usually do the chewing for their 
kinsmen or guests, or out of courtesy for others. Older youths or young men 
mix, wash, and wring the kava from the chewed pulp. Girls and women may 
occasionally participate in the chewing, whereas this was not so in the past. 
Adolescents and, more rarely, women may drink kava without censure. It is 
drunk in various places within the village proper, usually in a quiet house, 
and strict exclusion of children and women from the proximity and view of 
the proceedings has lapsed. Thus, the current kava drinking on Tongariki is 
more like that of the early John Frum movement on Tanna in its lack of 
formality and restraints. On Tanna, however, by the 1950's kava usage had 
returned essentially to the old traditional ceremonially controlled forms. 

Usually, half of a cocoanut shell or a bowl of the same capacity is used to 
prepare the kava and the full contents — about 100 ml. — drunk slowly in one 
draught. Sometimes twice this quantity is drunk. A kava drinker usually 
eats immediately after taking the kava; the kava is prepared while the 
evening meal is being cooked. The effects come on in a half hour or less, and 
the drinking is thus usually postponed until food is ready. Those who have 
drunk the kava find a comfortable place to sit, often beside a dying fire in 
the dark house, where they remain hunched over and avoiding light and 
sound disturbances of all sorts. Conversation ceases, and slowly they fall 
into a kava-induced stupor, which is not true sleep. This stage occurs about 
an hour after drinking. From it they can be aroused by being addressed or 
gently shaken, but this ruins the effect they are seeking from the kava. A 



120 



few hours after they have drunk kava they arise and walk to their own 
houses to fall asleep promptly again; others remain where they have first 
"fallen". In early morning they appear fresh and without any "hangover"- 
like sequelae. Those whom we have seen walking a few hours after the drink- 
ing are usually somewhat ataxic, photophobic, and slowed in their reactions. 
A few who have had a higher dose are extremely ataxic and could return 
to their homes only with assistance from the children or myself. There is 
no belligerency or irritability — only a quiet and friendly somnolence asso- 
ciated with the weakness of the lower limbs and the accompanying ataxia. 

The drinkers reply rationally and are well oriented in time, place, and 
person ; they respond intelligently, even sometimes quickly, to complex ques- 
tions. Bright or moving lights, noise or other sound, touch, and even the 
subdued bustle of nearby activity annoy them, and the villagers of all ages 
have extreme respect for this. In discussions the kava users refer to a heavi- 
ness and weakness of their extremities, particularly of the feet and legs, and 
to an earlier paresthesia ascending from their feet to their trunk and described 
with such words as "numbness", "tingling", and "coldness". They demon- 
strate a tactful avoidance of the disturbance my questioning produces, a 
very subdued annoyance at my "breaking" their kava. I have taken pulse 
rates and blood pressure measurements on a number of kava drinkers at 
varying intervals from one to three hours after drinking and found no 
significant change in either from that observed on the same subjects during 
examinations in the da3i:ime, when they had had no kava for the preceeding 
eighteen hours or more. Respiration is shallow and regular; deep tendon 
reflexes remain intact. 

Of interest to us in our genetic studies has been the effects that kava might 
have on fertility, since it is quite evident that kava drinkers rarely engage 
in sexual activity on the nights when they drink. Interviews with the women 
substantiate this. There is no dearth of children on Tongariki, but the popu- 
lation is not increasing explosively as it is in some parts of the Pacific, and 
kava drinking may serve as an interesting means of birth control for the 
small island, which could be easily over-populated. 

Dam-Bakker, DeGroot and Luyken have suspected the use of wati, as 
kava is called in southwest New Guinea, as a possible cause of the infertility 
in the Marind-Anim people. Their studies on chronic kava administration 
to rats, however, failed to demonstrate any impaired fertility, but they admit 
that they hardly reproduced essential features of kava use in the human 
community in their rat experiments. 

Jean Guiart and I have occasionally taken kava with the natives, and 
have noticed subjectively little difference in the sequence of symptoms and 
reactions from those reported by many Pacific voyagers since Captain 
Cook's days. A few peculiar paresthesiae of the face, legs and arms — espe- 
cially of the legs — a slight feeling of numbness, tingling, coldness and then 
weakness, accompanied early by shorter flashes of warmth or flush, occurred 
during the first half hour after ingestion. We have boorishly "broken" our 
kava at times, and walked off to engage in other activities without noticeable 
impairment of motor or sensory function. This has been after rather low 



262-016 0-67— 10 



121 



doses. There is, with higher doses, a pleasant, relaxing, paresthesia-enjoying, 
refreshing state of somnolence without mental dulling which eventually 
leads to sleep. At times, members of our team have taken large doses — a 
large cocoanut shell full — and real weakness, even a paresis making walking 
impossible, has been present for several hours after ingestion. Such an over- 
dose left one of us slightly ataxic with a persistent feeling of weakness in the 
lower limbs on into the next morning. 

Several recent accounts report little or no pharmacological action from 
kava prepared from grated or pounded dried kava root and used socially 
or ceremonially on Fiji and Samoa. My own experience in drinking such 
kava in Fijian villages is the same lack of effect. It is this dried kava root 
that has entered commerce, particularly on Fiji, and I wonder whether it is 
not this product that has been used in the pharmacological and chemical 
laboratories. The freshly harvested root, prepared by chewing, appears to 
result in the more potent preparation, the effects of which I have described. 
The stronger physiological actions of the kava used on Tongariki and Tanna 
may well be from the use of freshly harvested root rather than dried root, 
but there is also the possibility that the chewing and salivary digestion that 
is used to break up the fibers and emulsify the ingredients may be responsible 
for the pharmacologically more potent product. It is also likely that a higher 
dose of active ingredients is taken on Tongariki, since a considerably more 
concentrated extract appears to be prepared ; far more root is used per indi- 
vidual drinker than on Fiji or Samoa. 

APPENDIX 

Historical and Ethnographic Accounts of Kava Usage 

AiTKEN, R. T. "Ethnology of Tubuai." Bernice P. Bishop Museum, No. 70, (Bayard 
Dominick Expedition, publication no. 19), Honolulu, Hawaii, 42, 1930. 

Beaglehole, E. and P. "Ethnology of Pukapuka." Bernice P. Bishop Museum, No. 150, 
Honolulu, Hawaii, 25, 1938. 

Beabdmore, E. "The natives of Mowat, Daudai, New Guinea." Journal of the Anthropo- 
logical Institute of Great Britain and Ireland, 19 : 460, 1889-90. 

Bevan, T. F. "Toll, travel, and discovery in British New Guinea." London, 258, 1890. 

BiEO, S. L. "Neu-Guinea (Astrolabe Bai)." Ethnograflsche Sammlung des Ungarischer 
Museums, 3: (Budapest), 102, 1901. 

BoUEGAKEL, A. "Des races de I'Oceanie Frangaise de celles de la Nouvelle-Calidonie. 
In particnlier, seconde partie." Memoirs de la Societe d'Anthropologie de Paris, 2 : 
403, 1865. 

Buck, P. H. "Samoan material culture." Bernice P. Bishop Museum, Honolulu, Hawaii, 

No. 75, 92, 140, 147-164, 545, 548, 641, 679, 1930. 
"Ethnology of Tongareva." Bernice P. Bishop Museum, No. 92, Honolulu, Hawaii, 

81,119-121, (April) 1932. 
"Ethnology of Manihiki-Rakanga." By Te Rangi Hiroa. Bernice P. Bishop, 

Museum No. 99, Honolulu, Hawaii, 1932. 
"Mangaian society." Bernice P. Bishop Museum, No. 122, Honolulu, Hawaii, 

1934. 

"Ethnology of Mangareva." Bernice P. Bishop Museum, No. 157, Honolulu, Hawaii, 

1938. 

"Arts and crafts of the Cook Islands." Bernice P. Bishop Museum No. 179, 

Honolulu, Hawaii, 18-20, 1944. 



122 



BtiHLEB, A. "Versuch einer Bevolkerungs-und Kulturanalyse auf den Admiralitat- 

sinseln." Zeitschrift fiir Bthnologie, 67 : 1-32, 1935. 
Burrows, E. G. "Ethnology of Futuna." Bernice P. Bishop Museum, No. 138, Honolulu, 

Hawaii, 200-204, 1936. 

■ "Ethnology of Uvea (Wallis Island)." Bernice P. Bishop Museum, No. 145, 

Honolulu, Hawaii, 75-76, 139-148, 1937. 
Christian, F. W. "The Caroline Islands." London, 86, 87, 100, 188-193, 211, 1899. 
Churchill, W. "Samoan kava custom." Holmes Anniversary Volume, Washington, 

53-64, 1916. 

Churchward, W. B. "My consulate in Samoa." London, 47-59, 313, 347, 348, 1887. 
CoLLocoTT, E. E. V. "Kava ceremonial in Tonga." Journal of the Polynesian Society, 
36 : 21-47, 1927. 

Cook, J. "A voyage to the Pacific Ocean." 3 Volumes, London, vol. 2 ; 145, 155-56, 1784- 
1785. 

Cornet, B. C. "The quest and occupation of Tahiti by emissaries of Spain in 1772-76" ; 

3 volumes. The Hakluyt Society, London. Second Series, Nos. 32, 36, 43. II : 85n, 130, 

159, 168, 208, 218, 281, 472; III : 6, 51, 52, 59, 1913-19. 
CUMMiNG, Constance F. G. "At home in Fiji." Edinburgh, 50-51, 1882. 
D'Albertis, L. M. "New Guinea, what I did and what I saw." 2 volumes, London ; II : 

197, 1880. 

Dam-Bakker, a. W. I. VAN, DeGroot, a. p. and Luyken, R. "Influence of wati (Piper 
methysticum) on the fertility of the male rats." Tropical and Geographical Medicine, 
10 : 68-70, 1958. 

Deihl, J. R. "Kava and kava-drinking." Primitive Man, 5 : 4, 61-68, 1932. 

"Position of women in Samoan culture." Primitive Man, 5 : 2 and 3, 25, 1932. 

DiLLiON, P. "Narrative of the discovery of the fate of La Perouse's expedition." 2 vol- 
umes, London, II : 42-52, 1829. 
DuBBAD, W. J. "Notes on Torres Islands." Oceania, 10 : 389-403, 1940. 

EiLBRS, Anneliese. "luseln um Ponape." Ergebnisse der Sudsee Expedition 1908-10. 

G. Thilenius, ed., Hamburg, Friederichsen, de Gruyter and Co., II, B-8, 103, 1934. 
Ellis, W. "Polynesian researches." J. & J. Harper, New York, IV : 277-278, 1833. 
Emerson, O. P. "The Awa habit of the Hawaiians." The Hawaiian Annual, Honolulu, 

Hawaii, 130-140, 1903. 
FiNSCH, O. "Samoafahrten." Leipzig, 61, 1888. 

"Siidseearbeiten (Abhandlungen des Hambergischen Kolonialinstituts) ," 14: 

1-605, Hamburg, 1914. 
Firth, R. W. "Primitive economics of the New Zealand Maori." New York, E. P. Button, 

1929. 

FoRNANDER, A. "Hawaiian antiquities and folk-lore." Editor T. G. Thrum, Memoirs of 
the Bernice P. Bishop Museum, Honolulu, Hawaii, VI : 72, 110, 112, 258, 260, 405, 471, 
505, 540, 1919-20. 

Foster, G. A voyage round the world in his Britannic Majesty's sloop. Resolution. Two 

volumes, London, 1777. 
Fox, C. E. "The Threshold of the Pacific." London and New York, 44, 67, 216, 1924. 
GiFFORD, E. W. "Tongan society." Bernice P. Bishop Museum, No. 61, Honolulu, Hawaii, 

156-170, 1929. 

Guiart, J. "Un siecle et demi de Contacts Culturels a Tanna, Nouvelles-Hebrides." 
Publication de la Soci^te des Oceanistes, No. 5. Musee de I'Homme, Paris 15-16, 246- 
254, 1956. 

Haddon, a. C. "Kava drinking in New Guinea." Man, 16: 145-152, (Oct.) 1916. 
Hambruch, p. "Die Kawa auf Ponape." Studien und Forschungen zur Menschen- und 

Volkerkunde, Stuttgart, 14 : 107-115, 1917. 
Hambruch, P., and Filers, Annaliese. "Ponape." Ergebnisse der Siidsee Expedition 

1908-10, 231-246, 1936. 
Handy, E. S. C. "The native culture in the Marquesas." Bernice P. Bishop Museum, 

No. 9 (Bayard Dominick Expedition, Publication No. 9), Honolulu, Hawaii, 202-203, 

1923. 



123 



Handy, E. S. C. "Polynesian religion." Bernice P. Bishop Museum, Honolulu, Hawaii, 
No. 34, 46, 136, 162-163, 173, 219, 322, 327-328, 1927. 

"History and culture in the Society Islands." Bernice P. Bishop Museum, Hono- 
lulu, Hawaii, No. 79, 20-21, 1930. 

"History and culture in the Society Islands." Bernice P. Bishop Museum, No. 79, 

Honolulu, Hawaii, 1931. 

Hawkesworth, J., Editor. "An account of the voyages undertaken by the Order of His 
B. Majesty for discoveries," II : 200, 1773. 

Henky, T. "Ancient Tahiti." Bernice P. Bishop Museum, Honolulu, Hawaii, No. 48, 531, 
538, 539, 562, 583, 587, 1928. 

HocAET, A. M. "Lau Islands, Fiji." Bernice P. Bishop Museum, Honolulu, Hawaii, No. 
62, 59-70, 108, 1929. 

Hough, W. "Kava drinking as practiced by the Papuans and Polynesians." Smithsonian 
Miscellaneous Collection, 2 : 85-92 (Aug. 6), 1904, Quarterly Issue, Washington, D.C., 
1905. 

Humphreys, C. B. "The southern New Hebrides. An ethnological record." Cambridge, 
1926. 

King, J. "A voyage to the Pacific Ocean." Second edition, 3 volumes, London, 3 : 126-127, 
1785. 

Kramer, A. "Die Samoa-Insel." Stuttgart, 1902. 

Ledyasd, J. "John Ledyard's journal of Captain Cook's last voyage." Munford, J. K., ed., 
with introduction by Hitchings, S. H. Oregon State University Press, Corvallis, Oregon, 
August 1777, Customs of Otaheite, 51, 1963. 

Lester, R. M. "Kava drinking in Yitilevu, Fiji." Oceania, 12:2, 97-121, 1&41; 12:3, 
226-254, 1942. 

Lewin, L. "Tiber Piper Methysticum (Kawa)." A. Hirschwald, Berlin, 60 pp., 1886. 

"Phantastica : narcotic and stimulating drugs ; their use and abuse." K. Paul, 

Trench, Trubner and Co., London, 215-225, 1931. 

Ling Shun-sheng. "A comparative study of kava drinking in the Pacific regions." Bulle- 
tin of the Institute of Ethnology, Academia Sinica, 5 : 77-96, 1958. 

Linton, R. "The material culture of the Marquesas Islands." Memoirs of the Bernice P. 
Bishop Museum, Honolulu, Hawaii, VIII : 5, 366, 1923. 

Lloyd, C. G. "The use of kava by the Samoan Islanders." Pharmaceutical Review, 
18: (June), 261-266, 1900. 

LoEB, E. M. "History and traditions of Nine." Bernice P. Bishop Museum, No. 32, 
Honolulu, Hawaii, 172, 1926. 

MacGregor, G. "Ethnology of Tokelau." Bernice P. Bishop Museum, No. 146, Honolulu, 
Hawaii, 151, 1937. 

MacGregor, W. "British New Guinea." Journal of the Anthropological Institute of Great 
Britain and Ireland, XXI : 76, 204, 1891-92. 

"British New Guinea : country and people." London, 73, 75, 1897. 

Mariner, W. "An account of the natives of the Tonga Islands." 2 Volumes, London, 1817. 
McFarlane, S. "Among the cannibals of New Guinea." 126, 1888. 

Melville, H. "TTPEE : a peep at Polynesian life. During a four months' residence in 
a valley of the Marquesas." New York, 194-195, 1857. 

Metraux, a. "Ethnology of Easter Island." Bernice P. Bishop Museum, No. 160, Hono- 
lulu, Hawaii, 159, 1940. 

Miklukho-Maclay, N. von. Bulletin of the Imperial Russian Geographical Society, 
X: ii, 1874. 

"Ethnologische Bemerkungen ueber die Papuas der Maclay-Kiiste in Neu-Guinea." 

Natuurkundig Tijdschrift voor Nederlandsch Indie, 35 : 71, 1875. 
Nevermann, H. "Admiralitats-Inseln." Ergebnisse der Siidsee Expedition 1908-10, II-A3, 

Hamburg, 40, 1934. 

"Kawa auf Neuguinea." Ethnos, 3 : 179-192, 1938. 

Parkinson, R. "Dreissig Jahre in der Siidsee." Stuttgart, 373, 1907. 



124 



Parkinson, S. "A journal of a voyage to the South Seas, in His Majesty's ship. The 

Endeavour (1768)," London, 37, 1784. 
Porter, D. "A voyage to the South Seas." London, 95, 1823. 

Pratt, M. A. R. "A kava ceremony in Tonga." Journal of the Polynesian Society, 31 : 198- 
201, 1922. 

PuKui, Mary K. (Wiggin). Translations in the Bernice P. Bishop Museum, Honolulu, 
Hawaii: 1) "Against Awa (Ka Blele)," 2) "The evils of Awa (Ke Au Okoa)," 3) "On 
Awa drinking (Ko Hawaii Ponoi)." 

RiESENBERG, S. H. "The cultural position of Ponape in Oceania." Dissertation for Ph. D., 
University of California, Berkeley, 1949. 

"The Ponapean aboriginal political structure." Smithsonian Institution, Wash- 
ington, D.C., 1967. 

Rivers, W. H. R. "The history of Melanesian society." 2 Volumes, Cambridge, 1914. 
Sarasin, F. "Ethnolgoie der Neu-Caledonier und Loyalty-Insulaner." 2 Volumes, 
Miinchen, 1929. 

Sarfbrt, E. "Kusaie." Ergebnisse der Siidsee Expedition 1908-10, Hamburg, II-B-XII, 
410-412, 1919. 

Smith, S. P. "Uea ; or Wallis Island and its people." Journal of the Polynesian Society, 

Wellington, 1 : 112, 115, 116, 1892. 
"Kava drinking ceremonies among the Samoans and a boat voyage round Opulu 

Island, Samoa." Journal of the Polynesian Society, supplement, 1920. 
Speiser, F. "Ethnographische Materialien aus den Neuen Hebriden und der Banks- 

Inseln." Berlin, 162-164, 1923. 
Steinmetz, E. F. "Piper methysticum : kava, kawa, yagona ; famous drug plant of the 

South Sea islands. Amsterdam, 46 pp., 1960. 
Thompson, Laura M. "Southern Lau, Fiji : an ethnography." Bernice P. Bishop Museum, 

No. 162, Honolulu, Hawaii, 68-72, 97, 109, 168, 1940. 
Thomson, B. "Savage Island, an account of a sojourn in Nine and Tonga." London, 95, 

97, 1902. 

"The Fijians : A study of the decay of custom." London, 1908. 

TiTcoMB, Margaret. "Kava in Hawaii." Journal of the Polynesian Society, 57 : (June), 
105-171, 1948. 

True, R. H. "Kava-kava." Pharmaceutical Review, Milwaukee, 14 : 2, 28-32, 1896. 

Tyebman, D. and Bennet, G. "Journal of voyages and travels (compiled by James Mont- 
gomery)." 3 volumes, 2: 43, Boston, 1832 (from London edition 1831). 

Vancouver, G. "A voyage of discovery to the North Pacific Ocean, and round the world." 
3 volumes, London, 1 : 116, 1798. 

Williamson, R. W. and Piddington, R. "Essays in Polynesian ethnology." Cambridge, 
1939. 



125 



Chemistry of Kava 



MURLE W. KlOHS 

Riker Laboratories, Northridge, California 

Kava (/) is one of the popular names for the intoxicating drink prepared 
from the roots of the plant Piper methystioum Forst. by the inhabitants of 
the South Pacific Islands. The interesting tranquilizing properties ascribed 
to this romantic brew has prompted numerous chemical investigations over 
the last century, in the search for the physiologically active principles. These 
investigations have resulted in the isolation of a series of closely related sub- 
stituted 5,6-dihydro-a-py rones (Fig. 1), members of which have been shown 
to possess some of the actions on the central nervous system exhibited by the 
Kava extract, and a series of substituted a-pyrones (Figs. 2 and 3) which are 
relatively inactive in the test system employed. 

The first of the compounds to be isolated in the 5,6-dihydro-a-pyrone series, 
methysticin, was reported by Cuzent in 1861, followed in turn by Winzhei- 
mers isolation of dihydromethysticin in 1908. The most extensive investiga- 
tion of this plant, however, was carried out by Borsche and coworkers, who 
reported their findings in a series of fourteen papers published between 1914 
and 1933. This work covered the isolation of Kawain and dihydrokawain,- 
and their structural elucidation along with that of methysticin and dihydro- 
methysticin. (Figure 1) 




OCH3 OCH3 



Kawain Dihydrokawain 

Fig. 1 

Yangonin (Figure 2) was isolated by Reidel in 1904, and the y-pyrone struc- 
ture (I) was proposed by Borsche. This stood as the only naturally occurring 
2-methoxy-y-pyrone derivative until 1958 when Chmielewska, on the basis 
of spectral data, revised the structure to that of an a-pyrone (II). Secure 
support for these spectroscopic deductions has now been established by the 
unambiguous synthesis of yangonin by Bu'Lock and Smith. 



126 




Fig. 2 

In more recent times subsequent investigators have added four new com- 
pounds to the a-pyrone series, with the isolation of 5,6-dehydromethysticin, 
desmethoxyyangonin, 11-methoxyyangonin and 11-methoxynoryangonin (^) 
(Figure 3). The Structures of these compounds have been confirmed by 
synthesis. 




I l-Melhoxyyangonin I l-Mefhoxy-nor-yangonin 

Fig. 3 



With the structures of a physiologically active series of natural products 
established and the synthesis of analogues feasible, it is only natural for the 
medicinal chemist and pharmacologist to turn next to a molecular modifica- 
tion program to seek an optimum relationship between structure and activity. 
In studies with this objective in mind, which were carried out in our labora- 
tory some twelve years ago, the physiological activities of the naturally 
occurring compounds (Table I) that had been isolated at that time were 
used as the base line for comparison with the activities of the synthetic ana- 



127 



logues. In these experiments the compounds were administered orally to mice 
in a 10% Tween suspension, and screened initially for their effect on the cen- 
tral nervous system as determined by their ability to antagonize strychnine 
induced convulsions and death, cause fall out in the roller cage experiments, 
and potentiate sodium pentobarbital induced sleeping time. 



wOfnpouna 






Roller 




SIq ooin o 


tifne 








dose 




doso 


In % 




ffifl / K a 




fng / Kg 


result 


fftg / Kq 


controls 


Oihydrokowoin 


340 (270-430) 




300 no 


effect 


160 


150 


Yangonin 


no protection ot 


1,000 


300 no 


effect 


160 


150 


Kawain 


215 (160-290) 




300 no 


effect 


160 


235 


Dcsmethoxy yangonin 


no protection ot 


200 


300 no 


effect 


160 


130 


Methytticin 


160 (110-232) 




300 no 


effect 


160 


250 


Oihydromsthysticin 


115 (97-152) 




300 no 


effect 


60 


413 


Chloroform •itract 


140 (121-162) 




300 12/18 


160 


340 


Ground root 


1,700 (1,400-2.100) 


10,000 


12/16 


10,000 


400 



Table I 



On the basis of these results it can 'be seen that the crude extract, methy- 
sticin and dihydromethysticin were particularly effective in affording pro- 
tection against the lethal effects of strychnine. Using "fall-out" from revolv- 
ing cages as an index, none of the crystalline compounds had significant 
activity which is in sharp contrast to the ground root and the crude extract. 
On the basis of this latter test it would seem reasonable to say that there are 
compounds present in the extract possessing this activity which have not as 
yet been isolated. Dihydromethysticin proved to be the most potent agent in 
increasing the pentobarbital-induced sleeping time, showing good activity 
at 60 mg/kg whereas the other compounds were only slightly or moderately 
active at 160 mg/kg. 

The physiological activity observed with methysticin and dihydromethy- 
sticin as compared to yangonin and desmethoxy yangonin, indicated the 
importance of the 5,6-dihydro-a-pyrone ring to overall activity, and this was 
corroborated further by the complete loss of activity observed in the three 
test systems on opening the lactone ring of methysticin to yield methysticic 
acid (Figure 4). 

With this knowledge on hand a number of Ce substituted 5,6-dihydro-a- 
pyrone derivatives were prepared (3) by the Reformatsky condensation of the 
appropriate aldehyde and methyl-y-bromo-/8-methoxycrotonate, using the 
conditions as previously employed in our synthesis of dl-methysticin (Figure 
5). 



128 



OCHj 

dl — methytticin 

KOH 
(MeOH) 

CH=CH — CH=CH — C=CH— COOH 

I 

OCH3 

m«thysticic acid 

Fig. 4 





OCH1 



CH-CH-CHO + BrCHg-C^CH — COOCH3 



3, 4 — mefhylenedloxy 
cinnomaldehyd* 



"iT— bromo - /-msthoxy- 
mathyicrotonata 



THF -Zn ^ 




CH-CM- 



=0 



OCH, 



dl — mtthyiticin 

Fig. 5 



In the first series of analogues (Table II) , the ethylene bridge of dihydro- 
methysticin was omitted as represented by compound 2, and methoxyl groups 
were substituted in place of the ethylenedioxy group as shown by compounds 
3 and 4. These screening results would indicate that the methylenedioxy group 
is the preferred substituent and that the loss of the ethylene group causes a 
decrease in activity over dihydromethysticin as measured by its ability to 
inhibit strychnine convulsions and potentiate barbiturate sleep time. There 
is an indication, however, of activity in the roller cage where dihydromethy- 
sticin is inactive. 

The effect of varying the ethylene bridge on activity is shown in Table III. 
The first and second compounds, where the bridge has been lengthened to 
butylene and butadienyl respectively, showed little activity with the excep- 
tion of sleep time potentiation with the butylene analogue. The third com- 



129 





Q 


Strychnine 


Roller 


cage 


Sleeping 


time 




ED5Q+ 95% C L 


dose 




dote 


in % 




T 




fDQ / Kg 


result 


fng / Kg 


controls 




OCH3 












1. 




470 (375-590) 


300 


7/18 


160 


240 






260 (210-320) 


300 


5/18 


160 


472 




Cr 


950 (680-1480) 


300 


5/18 


160 


152 
















H3CO 




no protection 
ot 500 


300 


3/18 


160 


165 




0CH3 













Table II 



"1 


0- 

0CH3 


Strychnine 
mg/Kg 


Roller 
dose 

nf>g/Kg 


cage 
result 


Sleeping 
dose 

mg/Kg 


time 
in % 
controls 




P^(CH2)3-CH2- 


no protection 
at 500 


300 


1/18 


160 


536 




j^^^^(CH=CH )2- 


50% protection 
at 500 


300 


0/18 


160 


115 






no protection 


300 


3/18 


20 


283 






60% protection 


300 


10/18 


60 


304 



130 



Table III 



pound, in which a methyl group has been introduced on the carbon adjacent 
to the pyrone ring of dihydromethysticin, gave no protection at 500 mg/kg 
against strychnine, slight activity in the roller cage, and the highest activity 
of all the compounds in the potentiation of sleep time. The last compound, 
which is the corresponding analogue of methysticin, evidenced some activity 
in protecting against the effects of strychnine at 500 mg/kg, but good activity 
was observed in the roller cage and the potentiation of sleep time. 

The last series of compounds (Table IV) represent a more radical depar- 
ture from the structure of dihydromethysticin. In the first compound, where 
R is 3,4-methylenedioxyphenylethyl and is methyl, there was no protection 
obtained at 500 mg/kg against strychnine, moderate activity in the roller cage, 
and activity exceeding that of dihydromethysticin in the potentiation of sleep 
time. In the second compound where R is phenyl and R^ is methyl, there was 
again no protection afforded against strychnine at 500 mg/kg, there was good 
activity in the roller cage and moderate activity in sleep time potentiation. 
In the last compound, where both R and R^ are phenyl, no significant activity 
was observed in the first two tests and moderate activity was realized in the 
potentiation of sleep time. 

All of the above synthetic compounds including dl-methysticin and dl- 
dihydromethysticin, with the exception of compounds 1 and 2 in Table III, 
were then screened against supramaximal electroshock at an oral dose of 770 
mg/kg. At this dose range only compound 1 in Table II, compounds 3 and 4 
in Table III, and dl-methysticin and dl-dihydromethysticin, showed signifi- 
cant activity, giving 50% protection or better. 

On reviewing the structure activity relationship observed in this series of 
compounds it is apparent that the 5,6-dihydro-4-methoxy-a-pyrone ring plays 



0CH3 


strychnine 
mg/Kg 


Roller cage 
300 mg/Kg 


Sleeping time 
dote in % 
mg/Kg control* 


R 


R" 








-CO"-"""' 


-CH3 


no protection 
at 500 


5/18 


20 250 


. 0 


-CH3 


no protection 
at 500 


10/18 


160 266 


. 0 


a 


no protection 
at 500 


3/18 


160 331 



Table IV 

131 



a key role in the physiological activities as evidenced by the loss of activity 
realized on opening of the lactone ring, or by the introduction of imsaturation 
in the Cs-Ce position. Rigid overall specificity for drug receptor interaction 
in this series is discounted, however, by the variations of substituents which 
can be substituted at Ce while retaining activity in one or more of the test 
systems employed. 

REFERENCES 

(1) References to the work covered in this paper may be found, unless otherwise cited, 

in three recent reviews : (a) Keller, F., and M. W. Klohs, Lloydia, 26 : 1-15 (1963) ; 
(b) Mors, W. B., M. T. Magalhaes and O. R. Gottlieb. In L. Zechmeister Progress 
in the Chemistry of Organic Natural Products, Vol. 20, Wien, Springer Verlag pp 
131-164; (c) Hansel, R., Deut. Apoteka ztg. 104 (15) : 459-64 (1964) and 104 (16) : 
496-501 (1964). 

(2) Hansel, R., H. Saver and H. Rimplee, Arch. Pharm. 299 : 507-511 (1966) . 

(3) Tanabe, M., J. BoLGEE, F. J. Petbacek, F. Kellee, M. W. Klohs and G. B. Ceonheim, 

Unpublished work from these laboratories. 



132 



Pharmacology of Kava 



Hans J. Meyer 

Department of Pharmacology, University of Freiburg, Germany 

Pursuant to a continuing study of the pharmacological properties ot 
the Kava rhizome (Piper methysticum Forst), the six Ce-aryl-substituted 
alpha-py rones kawain (K), dihydrokawain (DHK), methysticin (M), 
dihydromethysticin (DHM), yangonin (Y), and desmethoxyyangonin 
(DMY) isolated from the rootstock, were further investigated in attempts 
to bring the central nervous and peripheral effects observed in man after 
consumption of Kava preparations (Forbes 1875, Kesteven 1882, Thomson 
1908, Deihl 1932, Leclerc 1937, Van Esveld 1937, Van Veen 1938, Titcomb 
1948, Frater 1968) in relation to adequately characterized constituents of 
the plant. Major interest Avas attributed to the question, in how far these 
substances can be regarded as the active principles of the drug. 

Because of low water solubility the pyrones were dissolved in peanut 
oil for the intraperitoneal and oral route of application. For intravenous 
injections and on isolated organs polyethylene glycol (Carbowax) 300 was 
employed. 

As is shown in FIG. 1, the absorption of K and DHK from the gas- 
trointestinal tract was remarkably rapid. The time of peak effect in mice 

100 r 



z 




0 10 20 30 60 90 120 180 

TIME IN MINUTES 



Fig. 1. — Duration of action of genuine Kava pyrones after oral administration in mice. 
Prevention of the tonic extensor component of maximal electroshock seizure (MES 
test). Corneal electrodes; square impulses of 50 mA, 60 Hz, 0.3 sec, 1 msec. Each point 
represents the mean of 15 animals. Doses employed: 150 mg/kg of kawain (K) and 
dihydrokawain (DHK), 70 mg/kg of methysticin (M) and dihydromethysticin (DHM) . 
Notice the rapid onset of K and DHK action as compared to that of M and DHM, 
the latter being about twice as effective when given orally. 



133 



proved to be 10 min as judged by the MES test. M and DHM have a longer 
induction period (30^5 min) and an appreciably longer duration of action 
in equieffective doses. 

The most characteristic central nervous action of all Kava pyrones, in- 
cluding Y and DMY, was shown to be their ability to produce a mephenesin- 
like muscular relaxation in all species of laboratory animals. According to 
Meyer and Kretzschmar (1966), who were the first to recognize this mecha- 
nism of action, Kava pyrones represent a new group of potent centrally 
acting skeletal muscle relaxants, the first of natural origin. Larger doses of 
the pyrones, with the exception of Y and DMY, produce ataxia and an as- 
cending paralysis without loss of consciousness, followed by complete re- 
covery. Pyrones were most effective when given intravenously (10-30 mg/ 
kg) ; the oral median paralyzing dose is some 10 times higher. In doses 
causing muscular relaxation and paralysis Kava pyrones did not possess a 
curare-like action on the myoneural junction (Meyer 1966). Death after 
large oral or intraperitoneal doses is the result of respiratory failure. 

Kava pyrones were found to depress polysynaptic responses such as the 
flexor, crossed extensor, skin twitch, pinna — prior to corneal — and linguo- 
mandibular reflexes in unanaesthetized animals. Effective doses ranged from 
20-40 mg/kg iv., whereas in anaesthetized animals corresponding doses were 
fomid to be 5-10 times smaller. An example is presented in FIG. 2, show- 
ing the depressant effect of 5 and 10 mg/kg of Y and DHM on the crossed 
extensor reflex in the anaesthetized guinea-pig. The normal knee jerk was 
aside from a transient increase in reflex magnitude little or not affected. 
Most sensitive to the pyrones proved to be the tonic stretch reflex (Meyer 
and Kretzschmar 1966). Thus, in unanaesthetized rabbits and guinea-pigs 
the tonic responses of alpha montoneurons to muscle stretch were either 




Fig. 2. — Effect of yangonin {Y) 5 and 10 mg/kg and dihydromethysticin {DHM) 6 mg/kg 
on the crossed extensor reflex. Guinea-pig, male, 740g. Urethane 1.0 g/kg intraperitoneally . 
Reflex elicited every 5 sec. Pyrones given intravenously in 30 sec. Stimulation of the 
afferent stump of sciatic nerve: 5.4 mA, 1 msec duration. Notice equipotency of Y 
and DHM relaxation of the quadriceps muscle indicated by the lowering of base line, 
and slower onset of Y action compared to that of DHM. Mi=miction. 



134 



DHM K Meph 

15 mg/kg 15 mg/kg 40 mg/kg 




I — I — I — I i I I I — I 1 1 — I — I — I — I — I — I — I — I I I : I I I ' ■ ' r f 

sec 



Fig. 3. — Inhibition of the tonic stretch reflex by dihydromethysticin (DHM), kawain (K), 
and mephenesin (Meph). Rabbit, male, 3.1 kg, unanaesthetized. Electromyograms of 
the quadriceps muscle, before and 1, 5, 10, and 20 min after injection. The injections 
were given intravenously with 2 hours interval. Time of stretch is indicated by points. 

abolished or restricted to an initial phasic response by 15 mg/kg of K 
or DHM intravenously. The action of mephenesin was about 3 times weaker 
and much shorter in duration (FIG. 3). Doses which produce decrease 
or block of spinal reflexes had little effect on the electroencephalogram 
(FIG. 4), and left EEG arousal from stimulation of the midbrain reticular 
formation unimpaired. 

In protecting mice from convulsions and death caused by toxic doses of 
strychnine Kava pyrones proved to be considerably more effective than 
mephenesin. Thus, complete protection from 4 mg/kg strychnine sulf . sc. was 
afforded by the intraperitoneal dose of 50 mg/kg of M, the most effec- 
tive of the pyrones, whereas mephenesin was ineffective in antago- 
nizing this degree of intoxication independent of the dose employed. 
With high doses of the pyrones (from 120 mg/kg intraperitoneally up- 
wards) there was a seizure syndrome of long periods of generalized clonic 
convulsions (15-17/sec) similar to that observed after barbiturates or 
meprobamate (Loewe 1958; Simon 1959). In addition, all six Kava pyrones 
were effective in depressing or abolishing the maximal tonic seizure induced 
by electroshock in mice. At the time of peak effect the following ED50 values 
(in mg/kg) were found after oral administration: 70 K, 98 DHK, 44.5 M, 



135 



vor Jnjaktion 



,\-^vnV'*V */i*:^'^r}^} ^«r^<^jA'^ .Vv*aU\vi^4-,V-'j^;\«'VwV/-^.^^ -.v 



Jnjektion von 40 mg/kg DHM i.v. 



3 min 

















10 min i , I ' I 



30 min 



90 min ill ""A^ 



Fig. 4. — Spontaneous cerebral cortex electrical activity in the unanaesthetized rabbit before 
and after injection of Ifi mglkg of dihydromethysiicin (DHM) intravenously. Duration 
of injection 100 sec. The dose produced complete paralysis. Bipolar electrodes on sen- 
somotor cortex. The records cover experimental periods of 5 sec each, obtained 3, 10, 
30, and 90 min after injection. 



< 

in 




OS W 2J) 



CONCENTRATION IN gV. 

Fig. 5. — Local anaesthetic activity of genuine Kava pyrones. Mean effective concentrations 
as established by the intracutaneous wheal method in guinea-pigs. The graph shows 
the relation between the concentration of the various pyrones (abscissae, logarithmic 
scale) and the average response from 6 animals for each concentration (ordinates). 
The dose was always injected in 0.25 ml of peanut oil, which proved to be inert. The 
response was tested 6 times in succession 1 min after injection. 



136 



50.5 DHM, 420 DMY, and 740 Y; by intravenous injection these figures 
were: 6.0 K, 6.1 DHK, 6.2 M, 8.1 DHM, 6.25 DMY, 11.5 Y, respectively, 
showing the striking difference in Y and DMY potency with the route 
of administration. Pyrone anticonvulsant activity and time course of action 
after intravenous administration were intermediate between mephenesin 
and procaine HCl with maximum effects 1 min after injection, made in 
15 sec. The effect produced by 10 mg/kg most commonly had worn off 
after 20 min. 

In addition to inducing changes in motor function, reflex irritability and 
seizure threshold and pattern (Meyer 1964), Kava py rones reduced the 
edema produced by formalin, serotonin, dextran, or carrageenin. Their anti- 
pyretic action is mild. Contractions of isolated ileum or uterus produced by 
histamine, barium, acetylcholine, bradykinin, 5-HT, or nicotine were in- 
hibited by the pyrones in concentrations of 1 :1.000.000 to 1 :100.000. This ap- 
plies to all pyrones, including DMY and Y. Kava pyrones posses local 
anaesthetic properties. Median anaesthetic concentrations as established by 
the intracutaneous wheal method in guinea-pigs (FIG. 5) increase in the 
following sequence: K 0.36%, M 0.37%, DHK 0.50%, DHM 0.60%, DMY 
1.0%, and Y>1.0%. Comparable values of procaine HCl, benzocaine and 
mephenesin were found to be 0.10%, 0.34% and 0.36%, respectively. In sur- 
face anaesthesia K was shown to be equipotent to cocaine HCl, when con- 
centrations of 0.5% were employed. Its duration of action was markedly 
longer than that of benzococaine (FIG. 6). Further details concerning the 
antiinflammatory, spasmolytic and local anaesthetic properties of the Kava 
pyrones were previously described (Meyer 1965a,b; Meyer and May 1964). 

As can be seen in FIG. 7, rapid intravenous injection of 10-30 mg/kg 
DHM causes a transient drop in blood pressure which depends on speed of 
injection and which was stronger in anaesthetized than in unanaesthetized 
rabbits. The mechanism underlying this action appears to be primarily the 
result of peripheral vasodilatation. In intact cats, rabbits and mice the blood 
pressure fall after DHM was followed by a characteristic bradycardia lasting 
several hours with a maximum reduction of heart rate by 40%. This effect was 
not observed in anaesthetized animals and was almost completely prevented 
by previous injection of atropine or bilateral vagotomy. No intravascular 
hemolysis was obtained in cats with solutions containing 20 mg/ml DHM 
or pyrone mixture. Oral or intraperitoneal administration of Kava pyrones 
had little or no effect on cardiovascular functions. 

It has been established that Y and DMY possess only weak central nervous 
activity when given orally or intraperitoneally. On intravenous injection and 
in experiments on isolated organs, however, the potency of both pyrones 
was shown to be of the same order of magnitude as observed with the other 
pyrones of the kavaroot, indicating poor absorption from the gut resp. 
peritoneum and/or rapid elimination of these materials. In further experi- 
ments it was found that the activity of orally or intraperitoneally admin- 
istered Y or DMY is markedly increased when given in combination with 
other pyrones. Both Y and DMY proved to be synergistic with all other 



262-016 0-67— 11 



137 




Kawain 
-° Benzocaine 
* Cocaine 



30 AO 50 60 

MINUTES 



70 



80 



90 



Fig. 6. — Surface anaesthetic action produced by kawain, benzocaine and cocaine HCl in 
the cornea of the rabbit. Concentrations tested were 0.5, 1.0, and 2.0%, respectively. 
Abscissa is time in minutes after instillation and ordinate is degree of anaesthesia in 
the range between zero and maximum possible effect (=36). Each point represents the 
mean of 6 animals. The corneal reflex was tested 6 times in succession at 5 min intervals 
until anaesthesia had worn ofif. Kawain and benzocaine were instilled in 0.25 ml of 
peanut oil, cocaine HCZ in saline. 

300 



250 



150 



< 

UJ 

m 



100 




HEART RATE 



30 mg/kg DHM i.v. 



15 20 25 

MINUTES 



(0 



45 



Fig. 7. — Responses of heart rate and femoral arterial pressure to the intravenous injection 
of SO mg/kg dihydromethysticin (DHM). Rabbit, female, 2.7 kg, unanesthetized. The 
injection was given in 30 sec. Systolic and diastolic blood pressure obtained before 
injection are indicated throughout the whole experiment by the broken lines showing 
the increment in amplitude under DHM. 



138 




mg/kg YAN60NIN i.p. 



Fig. 8. — Isobologram of combined yangonin-pyrone mixture effects in protecting mice from 
electrically induced convulsions {MES test). Abscissae: dose scale of yangonin (Yj, 
ordinates: dose scale of pyrone mixture (PM) consisting of methysticin, dihydro- 
methysticin, kawain, and dihydrokawain in equal parts. All injections were given 
intraperitoneally, Y and PM at the same time. Ratios of PM:Y tested were 4 : 1 to 
1: 6. Open circles indicate percentage of protected animals, triangles the mean effective 
doses (ED50). The isobole of combined doses having the same anticonvulsant effect 
(ED50) is represented by the line connecting the triangles. Rectilinear connection 
between ED50 of PM (26 mg/kg) and ED50 of Y (1.000 mg/kg) == isobole of addition. 
Y was without any effect when given alone in doses up to 300 mg/kg ip. 

pyrones studied in producing muscular relaxation, hypothermia or prevent- 
ing mice from MES (Meyer et al.) . This potentiation could be demonstrated 
in isobolometric experiments; an example is presented in FIG. 8. The greatly 
arcuate course of the isobole of median anticonvulsive doses running far 
below the rectilinear isobole of addition is characteristic of an effect more 
than additive. On the other hand, 5, 6-hydrogenated pyrones, behaved 
additive when given in combination. 

The experiments have shown that all the six known pyrones of the Kava 
rootstock are pharmacologically effective, differences in action being largely 
quantitative in nature. The finding that Y as well as DMY, contrary to all 
previous reports on this matter since the beginning of Kava investigation, 
represent biologically active principles especially on combined administra- 
tion with the other pyrones, is of particular interest in view of the relatively 
high amount of these two compounds in the kavaroot which is reported 
to be one quarter to one third of total pyrone content (Hansel and Beiers- 
dorff, 1959; Klohs et al., 1959). The synergism between Y and the other 
pyrones may provide an explanation for the high activity of a chloroform 
extract and of the crude root, reported by Klohs et al. (1959), which 
according to the authors was not evidenced by any of the pure isolated ma- 



139 



terials. The central nervous and peripheral activities of the pyrones as re- 
ported herein further substantiate the idea that the various etlinopharma- 
cological phenomena ascribed to Piper methysticum are due to the pyrone 
content of the plant. 

REFERENCES 
DiEHX, J. R. : Primitive Man, 5, 61 (1932) . 

FoKBES, L. : "Two Years in Fiji," London 1875, p. 190-195, 235-236. 
Featee, a. S. : Trans. Proc. Fiji Soc. Sci. Ind., 5, 81 (1958) . 
Hansel, R., and Beiersdorff, H. U. : Arzneimittelforsch., 9, 581 (1959). 
Kesteton, L. : Practitioner (London), 199-201 (1882). 

Klohs, M. W., Kellee, F., Williams, R. E., Toekes, M. I., and Ceonheim, G E. : 

J. med. pharmaceut. chem., 1, 95 (1959). 
Leleec, H. : Presse medicale. No. 9, 164 (1937) . 
LoEWE, S. : Arch. int. Pharmacodyn., 114, 451 (1958). 
Meteb, H. J. : Arch. int. Pharmacodyn., 150, 118 (1964) . 
Meteb, H. J., and May, H. U. : Klin. Wschr., 42, 407 (1964) . 
Meyer, H. J. : Arch. int. Pharmacodyn., 154, 449 (196oa) . 
Meter, H. J. : Klin. Wschr., 43, 469 (1965b). 

Meyer, H. J. : "Pharmakologie der Kawa-Droge- Zugleich ein Beitrag zum Problem des 

Kawa-Trinkens," HabUit, Schrif t, Freibui^ 1966. 
Meyer, H. J., and Keetzschmah, R. : Klin. Wschr., 44, 902 (1966). 
Meyer, H. J., et al. : In press. 

Simon, I. : Proc. I. int. congr. neuropharmacol., Elsevier 1959, p. 414. 

Thomson, B. : "The Fijians. A Study of the Decay of Custom," London 1908, p. 213, 
341-351. 

TiTCOMB, M. : J. Polynes, Soc., 57, 105 (1948). 

Van Esveld, L. W. : Ned. T. Geneesk., Si, 3961 (1937) . 

Van Veen, A. G. : Geneesk. T. Nederl. Ind., 78, 1941 (1938) . 



140 



Pharmacology of Kava' 



Joseph P. Buckley, Angelo R. Furgiuele, 
AND Maureen J. O'Hara 

Department of Pharmacology, School of Pharmacy 
University of Pittsburgh, Pittsburgh, Pennsylvania 

Piper methysticum Forst. (Piperaceae) is a perennial shrub indigenous 
to many islands of the South Pacific. Roots of this plant have been used by 
inhabitants of these islands to prepare a beverage known as Kava, Kawa, 
or Awa, which has been reported to allay anxiety and reduce fatigue (i, 2) . 
The pure crystalline alpha-pyrones, isolated from the roots of the plant 
which possess sedative-type activity, are soluble in the usual fat solvents but 
insoluble in water. Three of these, methysticin, dihydromethysticin, and 
dihydrokawain, possess sedative activity similar to that of the whole root 
{3^). Since Professor Meyer and his colleagues have worked extensively 
on the pharmacology of these water-insoluble a-pyrones, this present report 
will be concerned primarily with the pharmacological activity of water- 
soluble fractions of Kava. 

Experimental 

The plant material used was obtained from S. B. Penick Company, New 
York, New York, and consisted of finely pulverized root of P. methysticwn 
(Piperaceae). 

Steam Extraction 

One hundred grams of the finely pulverized root was mixed with approxi- 
mately 100 ml of distilled water giving a slurry having a volume of ap- 
proximately 200 ml. The slurry was steam distilled and the first 100 ml of 
distillate collected, filtered, and lyophilized. The yield for each extraction 
was approximately 50 mg of a yellow- white powder designated LE-1. Wlien 
this fraction was reconstituted in a cencentration of 10 mg/ml in distilled 
water, some of the material was insoluble and formed a fine suspension. 
Since preliminary studies on the spontaneous activity of mice indicated that 
both the filtrate and suspension possessed depressant activity, the following 
procedure was used to prepare subfractions. LE-1 was suspended in distilled 
water in a concentration of 20 mg/ml, shaken for 3 minutes. The mixture was 
then filtered through Whatman #1 filter paper, the filtrate shaken with 
two equivalent volumes of chloroform, the remaining aqueous solution 
lyophilized, and the resulting amorphous solid labeled Fj. The residue from 
the initial filtration was washed from the filter paper and made up to 15 ml 

1 This investigation was supported by a P.H.S. researcli grant MH-03029 from tlie National 
Institute of Mental Health. 



141 



with distilled water, shaken for 3 minutes, and filtered. The filtrate was 
collected and the remaining minute residue discarded. This filtrate was also 
washed with two equivalent volumes of chloroform and the resulting aqueous 
solution lyophilized and the amorphous solids labeled Fz. 

Pharmacological Studies 

Spontaneom and Forced Motor Activity Studies. — The effects of LE-1, 
Fi, and Fj, on spontaneous motor activity of male albino Swiss-Webster 
mice were evaluated in photocell activity cages as described by Furgiuele et 
al. (7). Fifty to 60 minutes after receiving an intraperitoneal injection of 
one of the fractions or saline, 1 hour prior to testing. Maximum per- 
activity cages (Actophotometer, Metro Industries, New York) and a 15 
minute count taken 10 minutes later. Each fraction was tested at 4 dose levels 
using 4 to 6 groups of 5 mice per group. The effects of the fractions on 
forced motor activity were investigated using the rotarod (^, 9). Each group 
was trained to walk a 1.5 inch diameter hardwood rod rotating at 15 rpm or 
a 1 inch diameter rod rotating at 29 rpm {10, 11). The mice were trained 
to walk the rotating rod and on test days received i.p. injections of either 
one of the fractions or saline, 1 hour prior to testing. Maximum per- 
formance time was set at 120 seconds for the 1 inch rod and 180 seconds 
for the 11/2 inch rod. 

Septal Rats. — LE-1 was investigated for possible antagonism of the 
exaggerated irritability and aggressiveness of rats having lesions in the 
septal area {12). Three to four days following production of the lesions 
behavioral abnormalities were scored as described by Schallek et al. {13). 
This involved scoring the responses obtained by (a) a puff of air on the 
back, (b) gently touching the whiskers with a probe, (c) gently prodding 
the animal's back with a probe, and (d) approaching the rat with a gloved 
hand. Each test was rated on a scale ranging from 0 for no response to 6 
for the most violent response. Different groups of 5 rats were tested, 0.5, 1, 
and 2 hours following intraperitoneal injection of fraction LE-1. Since 
chlordiazepoxide has also been reported {12) to be particularly effective in 
this preparation, it was compared to the activity of LE-1. The ED50 was 
determined graphically using the method of Miller and Tainter (-?^). 

Conditioned Avoidance Response. — The rat pole climbing procedure of 
Cook and Weidley {16) was modified for these tests {10). Each cycle con- 
sisted of 15 seconds of tone followed by a maximum of 30 seconds of shock, 
at 2.75 minute intervals and the number of times the animal responded to 
either tone or shock was recorded. Each animal was subjected to 2 to 3 
ten-cycle training sessions. Trained groups of 6 male albino Wistar rats 
received i.p. injections of either LE-1, 50, 100, and 200 mg/kg; chlordia- 
zepoxide, 10, 20, and 40 mg/kg; or saline, 0.1 ml, one hour prior to a 10 
cycle session. The number of times that the rat failed to respond to tone 
but did respond to shock was a measure of the inhibition of the conditioned 
response. 



142 



Electroencephalographic Studies. — Cats with chronically implanted cor- 
tical and subcortical electrodes were ^prepared as described by Horovitz and 
Chow {16). Bipolar electrodes were implanted into the amygdala (AP=13, 
L=9, H=5), hippocampus (AP=5, L=12.5, H=1.5), and pontine reticular 
formation (AP = 35 mm anterior to F=0, L=0, H=32 mm at an angle 
of 25 degrees) according to the atlas of Jasper and Ajmone-Mai-san {17) 
and into the posterior hypothalamus (AP=9, L=0.5, H=2.5) according to 
the atlas of Bleier {IS). Monopolar electrodes were placed over appropriate 
cortical areas, 5 to 10 mm apart. Simultaneous recordings were obtained from 
three different leads onto a Grass polygraph. A Grass square-wave stimulator 
was used to stimulate the posterior hypothalamus or brain stem reticular 
formation for a period of 15 seconds with pulses of 100 c.p.s. having a dura- 
tion of 5 msec and at 0.5 to 8.5 volts. The animals were placed in a semi- 
soimdproof constant environment chamber fitted with a one-way glass win- 
dow and a small light. The animals were fed, placed into individual chambers, 
and allowed a period of one hour to acclimatize. Control recordings were 
obtained and the threshhold for EEG arousal determined following the 
electrical, visual (blinking lights) or auditory (clap) stimulation. A desyn- 
chronization of the resting EEG for a period of approximately twice the 
duration of the stimulus or longer was taken as the arousal response. The pos- 
terior hypothalamus of two cats and the brain stem reticular formation of two 
other cats were stimulated and cortical and subcortical activity recorded. 
After control recordings, the cats were removed from the chambers, and an 
aqueous solution of either LE-1 or clilordiazepoxide administered intraperi- 
toneally. The ejffects on spontaneous EEG activity and upon arousal were 
observed 30, 60, 120, and 180 minutes following administration. An interval 
of at least 5 days was permitted between injections to insure recovery of 
the test animals. At the termination of the study, the animals were sacrificed, 
the brains perfused with 10% formalin and location of the electrodes verified. 

Antiserotonin Activity . — A rat uterine horn obtained from virgin rats 
(Wistar) in the estrus stage, as determined by microscopic examination of 
vaginal smears, was suspended in a 10 ml tissue bath containing modified 
deJ alon's solution ( 19) , containing calcium chloride, 20 mg/1, and oxygenated 
with 95% O2 and 5% CO2 at a temperature of 37.5°. Uterine contractions 
were recorded on a smoked kymograph drum via a muscle lever so that 
the magnification was approximately 3X. All test substances were added 
in volumes not exceeding 0.15 ml and the a-pyrones investigated were admin- 
istered in a suspension of 1% methylcellulose, 1500 cps. Maximal contrac- 
tion of the uterine horn was induced by serotonin creatinine sulfate, 0.5 to 
1.0 mcg/10 ml bathing solution. The dose producing maximal contraction 
was added to the bath every fourth minute; following the contraction the 
tissue was washed Avith fresh deJalon's solution. After two equivalent re- 
sponses to serotonin were obtained, a given quantity of one of the a-pyrones or 
subfraction Fi or F2 was added to the bath, 30 seconds prior to the next 
dose of serotonin. Additional doses of the antagonists were not added until 
the serotonin response had returned to normal. Equivalent volumes of 1% 
methylcellulose did not affect the response of the uterine horn to serotonin. 



143 



Effects on Brain Serotonin Content. — Dihydromethysticin, 100 mg/kg, 
Fi, 100 mg/kg, F2, 100 mg/kg, chlordiazepoxide, 5 mg/kg, and reserpine 
phosphate, 1.25 mg/kg were each administered to 5 mice. The animals were 
sacrificed one hour following i.p. administration by stunning and exsangui- 
nation. The brains were removed intact, weighed, and transferred to a 
glass homogenization tube containing sufficient 0.1 N HCl to make a total 
volume of 3.0 ml. The tissue was homogenized with a motor driven teflon 
homogenizer and the homogenate rinsed with 7.0 ml of glass distilled water 
and transferred to a 30 ml centrifuge tube containing 3.0 ml of borate 
buffer. Serotonin was extracted using the method of Bogdanski et al. {20) 
as modified by Aprison et al. {21) and serotonin concentration determined 
with a Turner fluorometer {22). 

Results 

PhysicciL-Ghemical Characteristics of Subfractions Fi and F2. — Subfrac- 
tion Fi was found to be 16 times more soluble in water than F2. The physical- 
chemical characteristics and average yield of Fi and F2 are summarized in 
Table 1. Nitrogen could not be detected in either fraction and aldehydes 
and/or ketones were detected in F2 only. 



Table 1. — Some -physical and chemical characteristics of subfractions Ft and Ft from the 

lyophilized steam distillate of Kava 



Property 


F, 


F2 


Physical state 


Amorphous solid 


Amorphous solid 


Color 


Amber 


Yellowish white 


Odor 


Aromatic 


Aromatic 


Sodium Fusion 


Nitrogen absent 


Nitrogen absent 


Ignition 


Burned with a sooty flame, 


Burned with a sooty flame, 




small residue 


no residue 


Solubility 


8 mg/ml 


0.5 mg/ml 


Av. yield 


60 mg/200 mg LE-1 


18 mg/200 mg LE-1 


2, 4-Dinitrophenylhy- 


No dinitrophenylhydra- 


Red needle shaped crystals 


drazine 


zone formed 


of insoluble dinitrophenyl- 






hydrazone formed 



Sfontaneous and Forced Motor Activity. — The effects of the aqueous 
fractions from Kava on spontaneous motor activity of mice are sum- 
marized in Table 2. LE-1, Fi, and F2 depressed spontaneous motor activity 
in a dose-related manner. The estimated ED50 for Fi being 31.6 mg/kg 
and F2 6.4 mg/kg. Loss of righting reflex was not observed even at those doses 
which almost completely abolished spontaneous motor activity. Doses of the 
fractions showing marked inhibition of spontaneous motor activity did not 
alter the forced motor activity of mice placed on the rotarod. 

Septal Rats. — The effects of LE-1 and clilordiazepoxide on the hyper- 
irritability of septal rats are summarized in Table 3. LE-1 was approxi- 



144 



Table 2. — Effects of lyophilized aqueous kava on spontaneous motor activity of mice 



Fraction 


I. P. Dose 
(mg/kg) 




l-J i 5 0 ^ 1 "1 4- Q f Y"fl 

JT crCcll UdgC 

Inhibition 
Photocell 
Activity 


LE-1 


42 


6 


67 




84 


6 


77 




1 OA 


D 


sy 




240 


0 


yi 


F, 


5 


4 


14 




10 


4 


28 




OK 

Jo 


A 

4 


00 




50 


4 




F2 


5 


4 


47 




10 


4 


59 




25 


4 


84 




50 


4 


92 



» Number of groups, 5 mice/group. 



mately one-tenth as effective as chlordiazepoxide in reducing the hyper- 
irritability of these animals ; however, even the 50 mg/kg dose significantly 
affected the experimental animals and ataxia was not observed in those 
animals receiving doses as high as 200 mg/kg of LE-1 whereas moderate to 
marked ataxia occurred at the 20 and 40 mg/kg doses of chlordiazepoxide. 

Conditioned Avoidance Response. — LE-1 in doses ranging from 50 to 400 
mg/kg i.p. produced a significant inhibition of the CAR which was dose de- 
pendent. The ED50 for LE-1 was 82 mg/kg and for chlordiazepoxide 21 mg/ 
kg. (see table 4) . LE-1 did not inhibit the shock response whereas chlordiaz- 
epoxide, 40 mg/kg, did produce a significant reduction in shock responses. 

Electroencephalographic Studies. — The effects of LE-1 on the duration 
of the arousal response after threshold stimulus are summarized in Table 5. 



Table 3. — Effects of LE-1 and chlordiazepoxde on the rage score of septal rats 



Drug 




Dose (mg/kg, 
i.p.) 


Mean Score ± S.E. 


ED JO ± percent 
S.E. (mg/kg) 


Control 


20 




62±3 




LE-1 


5 


50 


47±6b 






5 


100 


37±6b 


170±19 




5 


200 


26±6'' 




Chlordiazepoxide 


5 


10 


48±3b 






5 


20 


26±12'' 


17±20 




5 


40 


14±2b 





» N, number of rats tested. 
Significantly different from controls (p<0.05). 



145 



Table 4. — Effects of LE-1 and chlordiazepoxide on the rat conditioned avoidance response 

(car) 







i.p. 


Percent 


ICR 60 ± 


Drug 




(mg/kg) 


Inhibition 


percent S.E. 






of CAR 


(mg/kg) 


Control 


24 




8 




LE-1 


6 


50 


MS 






6 


100 


•> 65 


82±31 




6 


200 


b 70 






6 


400 


'>92 




Chlordiazepoxide 


6 


10 


b 26 






6 


20 


b 37 


21 ±14 




6 


30 


>'64 






6 


40 


100 





» N, number of rats tested. 

^ Significantly different from controls (p<0.05). 



Table 5. — Effects of LE-1 on duration of arousal following threshold stimulation in cats 











Duration of Aroi sal, Seconds 


Cat 


i.p. 


Area 


Area 












No. 


(mg/kg) 


Stimulated 


Recorded 


















0 hr » 


0.5 hr 


1 hr 


2 hr 


3 hr 


4 


50 


Ret. Form. 


P. Sigmoid 


32 


20 


15 


30 










A. Suprasyl. 


32 


20 


15 


30 










P. Hypothal. 


32 


20 


15 


30 




3 


50 


P. Hypothal. 


P. Sigmoid 


25 


13 


9 


22 










A. Suprasyl. 


25 


13 


9 


22 










Amygdala 


25 


13 


9 


22 




2 


50 


P. Hypothal. 


A. Sigmoid 


40 


30 


21 


35 










P. Sigmoid 


40 


30 


24 


35 










Amygdala 


40 


30 


21 


35 




1 


100 


Ret. Form 


P. Sigmoid 


29 


0 


0 


16 


22 








A. Suprasyl. 


29 


0 


0 


16 


22 








P. Hypothal. 


26 


0 


0 


10 


29 


4 


100 


Ret. Form. 


P. Sigmoid 


42 


10 


0 


0 


36 








A. Suprasyl. 


42 


10 


0 


0 


39 








P. Hypothal. 


48 


10 


0 


0 


48 


4 


150 


Ret. Form. 


P. Sigmoid 


60 


0 


0 


0 


bO 








A. Suprasyl. 


50 


10 


0 


0 


''37 








P. Hypothal. 


50 


2 


0 


0 


bO 


2 


150 


P. Hypothal. 


A. Sigmoid 


37 


(<=) 


10 


0 


12 








P. Sigmoid 


37 


(») 


10 


0 


11 








Hippocampus 


37 


C) 


10 


0 


12 



* Predrug. 

b Recovery in 4 hours. 
" Unable to record. 



146 



The lowest dose of LE-1 shortened the duration of the arousal response for 
approximately one hour. Although this effect was observed in recordings 
from both cortical and subcortical sites, no significant changes in the EEG 
activity were evident. The larger doses of 100 and 150 mg/kg effectively 
blocked EEG arousal and caused a slowing of spontaneous cortical and sub- 
cortical activity. Mild to marked ataxia occurred following the 100 and 150 
mg/kg doses, respectively. The duration of the arousal response after audi- 
tory stimulation was unaffected at the 50 mg/kg dose and shortened after 
100 mg/kg and completely abolished following the 150 mg/kg dose of LE-1. 
The EEG arousal induced by visual stimulation was unaffected at the 50 mg/ 
kg dose, shortened somewhat following 100 mg/kg, and blocked for more 
than 2 hours following the 150 mg/kg administration of LE-1. Moderate 
ataxia was observed in those cats receiving 150 mg/kg and was still evident 
12 to 14 hours after drug administration. 

Chlordiazepoxide effectively reduced cortical and subcortical arousal in 
doses ranging from 5 to 15 mg/ kg, i.p. In two cats, chlordiazepoxide induced 
a period of excitation of sufficient intensity that recording was prevented. 

Antiserotonin Activity. — Desmethoxy-yangonin, dihydromethysticin, ka- 
wain, and Fa antagonized the serotonin induced contractions of the isolated 
rat uterus whereas Fi did not alter the serotonin activity in doses ranging 
from 100 to 400 mcg/10 ml bath (Fig. 1). The ED50 (dose per 10 ml bathing 




IOO;ig 5q;jg 25>jg 
DMY DMY DWY 



Fig. 1. — Kymograph tracings showing the effects of (a) desmethoxy-yangonin (DMY), 
(b) Kawain (K) and (c) F, and Fj on serotonin induced contractions of the isolated 
rat uterus (from O'Hara, M. J., Kinnard, W. J., and Buckley, J. P., J. Pharm. Sci. 
54, 1021, (1965). 



147 



fluid inhibiting serotonin response by 50%) for desmethoxy-yangonin was 32 
meg, kawain 100 meg, dihydromethysticin 75 meg, and F2 225 meg. This 
antagonism of the a-pyrones to the serotonin induced contraction of the 
isolated rat uterus appears to be specific since dihydromethysticin failed to 
alter the contraction induced by either bradykinin or acetylcholine (see Table 
6 and Fig. 2) . 



Table 6. — Responses of an isolated rat uterus to dihydromethysticin showing specificity of 

antagonism to serotonin 



Serotonin 


Acetylcholine 


Bradykinin 


DHM 


Contraction 


(meg/ 10 ml) 


(mcg/10 ml) 


(ng^/10 ml) 


(mcg/10 ml) 


(cm) 


1. 0 


0. 0 


0 


0 


4 5 


1. 0 


0. 0 


0 


100 


1. 4 


0. 0 


5. 0 


0 


0 


7. 2 


0. 0 


5. 0 


0 


100 


7. 2 


0. 0 


0. 0 


400 


0 


7. 8 


0. 0 


0. 0 


400 


100 


7. 8 



" ng., nanogram. 




Fig. 2. — Kymograph tracings showing the effects of dihydromethysticin (DHM) on (a) 
serotonin, and (b) bradykinin (br) and acetylcholine (ac) induced contraction of the 
isolated rat uterus (from O'Haj-a, M. J., Kinnard, W. J., and Buckley, J. P., J. Pharm. 
Sci. 54, 1021, (1965). 



Brain Serotonin. — Brain levels of endogenous serotonin were not altered 
1 hour after the i.p. administration of dihydromethysticin, Fi, F2 and chlor- 
diazepoxide. Reserpine reduced brain serotonium levels by 27%. 



148 



Discussion 



LE-1, a lyophilized steam distillate of PJ,per methysticum Forst., and the 
two water soluble apparently distinctive subfractions of the distillate pro- 
duced marked depression of spontaneous motor activity of mice without 
altering the rotarod performance. Chromatographic data indicated that the 
pharmacological actions of this fraction were due to substances other than 
the known a-pyrones {10) . LE-1 reduced the behavior abnormalities of septal 
rats in a manner similar to that of chlordiazepoxide in doses which exerted a 
specific blockade of the conditioned avoidance response. King and Meyer 
{23) have postulated that in the rat the septal area normally acts to dampen 
hypothalamic Output, associated with an emotional state, whereas the amyg- 
dala may facilitate this hypothalamic activity. Destruction of the septal 
areas should remove its restraining influence and result in a hyperirritable 
animal. Schallek et al. {13) theorized that the reduced activity in the amyg- 
dala is related to the psychodepressant effects of chlordiazepoxide. 

LE-1 caused moderate slowing of cortical, hypothalamic, and hippo- 
campal activity with concomitant ataxia and motor deficiency. After cortical 
activity had returned to pretreatment levels, subcortical (hypothalamic and 
hippocampal) activity was still reduced, evidenced by the absence of EEG 
arousal. Although return of the arousal pattern generally marked the end 
of an experiment, ataxia and uncoordinated movements were still present, 
an indication that LE-1 was exerting a skeletal muscle relaxant effect. Ataxia 
was one of the most consistent responses obtained with LE-1 in mice and rats 
(with the exception of septal rats) also suggesting skeletal muscle relaxant 
activity. A single intravenous dose of 20 mg/kg of LE-1 completely blocked 
the flexor reflex for approximately 3 hours in two cats. It appears that at 
least part of the altered behavioral effects observed in mice and rats as well 
as cats could be due to blockade of the spinal interneurons, with progressive 
weaker depressant effects on the reticular formation, subcortex, and cortex 
respectively. Certain of the a-pyrones exhibited a dose-related antagonism of 
the serotonin-induced contraction of the rat uterus and exhibited potency 
comparable to N-(/3-dimethylaminoethyl) cinnamamide (^^). The a-pyrones 
isolated from Kava possessing this antiserotonin activity have a cinnamoyl 
moiety which may be responsible for this particular pharmacological action. 
Antiserotonin studies further substantiated the difference in activity between 
Fi and F2 in that Fi did not affect the serotonin response whereas F2 was 
antagonistic to it. Subfraction Fj was a much weaker depressant on a weight- 
weight basis than subfraction F2. Since thin-layer chromatograms demon- 
strated that Fi is absolutely free of. known a-pyrones (Fig. 3) and since the 
overall pharmacological profile may be quite different than that of F2, studies 
are currently being undertaken to isolate the pharmacologically active con- 
stituents in this more water soluble subfraction. 



149 




lOO^g 



100 pg 



100 yg 



Fig. 3. — Thin layer chromatogram of certain aqueous fractions of Kava (from O'Hara, 
M. J., Kinnard, W. J., and Buckley, J. P. J. Pharm. Sci. 54, 1021, (1965). 



REFERENCES 



( 1 ) ScHUBEL, K., J. Soc. Chem. Ind. 43, 766 ( 1924 ) . 

(2) Van Veen, A. G., Rec. Trav. Chim. 58, 521 (1939). 

(3) Van Veen, A. G., Tijdsehr. Nederland India 78, 1941 (1938). 

(//) Klohs, M. W., Keller, F., Williams, R. E., Tokes, M. I., and Cronheim, G. E., 
J. Med. Pharm. Chem. 1, 95 (1959) . 

(5) Meyer, H. J., Arch. Int. Pharmacodyn, 116, 45 (1958). 

(6) Keller, F. and Klohs, M. W., Lloydia 26, 1 (1963) . 

(7) Furgiuele, a. R., Kinnard, W. J., and Buckley, J. P., J. Pharmacol. Exp. Therap. 

137,356 (1962). 

(8) Kinnard, W. J. and Carr, C. J., J. Pharmacol. Exp. Therap. 121, 354 (1957). 

(9) Watzman, N., Barry, H., Buckley, J. P., and Kinnard, W. J., J. Pharm, Sci. 53, 

1429 (1964). 

{10) Furgiuele, A. R., Kinnard, W. J., Aoeto, M. D., and Bucklet, J. P., J. Pharm. Sci. 
54,247 (1965). 



150 



(11) O'Haea, M. J., KiNNARD, W. J. and Buckley, J. P., J. Pharm. Sci. 54, 1021 (1965). 

(12) Randall, L. O., Schallek, W., Heise, G. A., Keith, E. F., and Bagdon, R. E., J. 

Pharmacol. Exp. Therap. 129, 163 (1960). 

(13) Schallek, W., Kuehn, D., and Jew, N., Ann. N.Y. Acad. Sci. 96, 303 (1962). 
(J4) Miller, C. L. and Tainter, M. L., Proc. Soc. Exp. Biol. Med. 57, 261 (1944). 

(15) Cook, L. and Weidley, E., Ann. N.Y. Acad. Sci. 66, 740 (1957). 

(16) HoROviTZ, Z. P. and Chow, M., J. Pharm. Sci. 52, 198 (1963). 

(17) Jasper, H. H. and Ajmone-Marsan, C, "A Stereotaxic Atlas of the Diencephalon 

of the Cat", The National Research Council of Canada (1960). 

(18) Bleter, R., "The Hypothalmus of the Cat", The Johns Hopkins Press, Baltimore 

(1961). 

(19) Burn, J. A., "Practical Pharmacology", Blackwell Scientific Publications, Oxford, 

England, p. 13 (1952). 

(20) BoGDANSKi, D. F., Pletscher, a., Brodie, B. B., and Udenfriend, S., J. Pharmacol. 

Exp. Therap. 117, 82 (1956) . 

(21) Aprison, M. H., Wolf, M. A., Poulos, G. L., and Folkerth, T. L., J. Neurochem. 9, 

575 (1962). 

(22) Udenfriend, S., Weissbach, H., and Brodie, B. B., "Methods of Biochemical An- 

alyses", D. Click (ed.). Academic Press, Inc., New York, N.Y. p. 105 (1958). 

(23) King, F. A. and Meyer, P. M., Science 128, 655 (1958) . 

(24) DoMBRO, R. S. and Woolley, D. W., Biochem. Pharmacol. 13, 569 (1964). 



151 



Electropharmacological and 
Behavioral Actions of Kava 



Amedeo S. Marrazzi 

Department of Pharmacology, University of Minnesota Medical School, 
Minneapolis, Minnesota 



This compound in interesting for its consistencies, and I also want to 
make a point illustrating a concept of a potential mechanism of tranquilizer 
action. We first got interested in 1959, because of the descriptions and because 
of the confirmation of these descriptions by Dr. Franck of the American 
Medical Association Editorial Staff. 

I simply wanted to show you two slides, and I need to show you two 
older slides for reference. (Fig. 1 ) 




Maximum 
Effect 




100 cps 

Fig. 1 



In the first of these slides showing evoked cortical potentials in a cat, 
you see that a tranquilizer, in this case chlorpromazine (CPZ), prevents 
(2nd column) the cerebral synaptic inhibitory effect of LSD (1st column). 
It controls LSD. After the chlorpromazine has been dissipated, there is 
recovery (3rd column) and LSD again produces its cerebral action. This 
is one of the typical actions of a psychotogen, and we think that tran- 
quilizers have a similar but weaker action. The data actually then lend them- 
selves to the notion — and we have further data supporting it — that they 
have the same kind of action as the psychotogens, illustrated by LSD, but 
weaker, and therefore are able to compete for the same receptor. 

It seemed interesting to see what Kava would do under similar circum- 
stances. A preliminary water extract proved quite potent, and three-tenths 
of a cc given intracarotidly, elicited an affect very similar to that of 
LSD. {Fig. 2) 



152 



CONTROL MAXIMUM EFFECT RECOVERY 




100 '\; 

Fig. 2 



Obviously we are interested in the relation of an electrical effect in anes- 
thetized animals to the behavior that the nervous system controls. Fig. 3 is 
interesting in this connection. 

This happens to be a rat conditioned approach experiment, in which the 
response latency to the signal tone is indicated by the length of the upright 
lines. The effect of LSD is a prolongation of the response time. This would 
be expected from the synaptic inhibitory action. Inhibition of inhibition, 
i.e. disinhibition or a release phenomenon, occurs at smaller doses but is 
here masked by the over-riding over- all inhibition. I Avon't go into the 
chlorpromazine protection at the moment. 

This {Fig. 4) is the same kind of an experiment with Kava. There is a 
great prolongation in the response time. The sharp cut-off at the top is 
simply because the equipment turns off after twenty seconds without a 
response. 

It then seems interesting, in the first place, that this material is quite active, 
because that amount of synaptic inhibition is the equivalent of forty micro- 
grams of serotonin. 



in 
■o 
c 
o 
o 

to 



>- 
o 

Z 
LJ 



TIME 0 

mm 



CONTROL 



CHLORPROMAZINE (CPZ) 



0.030 mg/ko 

n Ji,)k,ii,JnlH4u-^ 




,11 III .ll 


I't 1 11 - '■ lH liJ ' 












IM, li 




>j-ULJ4-i-a-Mt III- 1 





















llJ 

CO 

o 

Q. 
CO 
UJ 

q: 



Rfl wards 
TIME 
mm 



Rewards 

TIME 

mm 



LYSERGIC ACID DIETHYLAMIDE (LSD-25) 



0.10 mg/kg 



llllillllli.l..l|H,.l..,l..l„l..l.„l I,, 



0.030 mg/kj- 



10 30 40 



PROTECTION BY CPZ 



CPZ LSD-25 



0.10 mg/kg 



Fig. 3 



262-016 0-67—12 



153 




Fig. 4 



In the second place, it acts like LSD on synaptic transmission and 
behaviorally, and you heard rather an extensive follow-up from Dr. Buckley 
and related data from Dr. Meyer. 

The point that I was trying to bring out is the possibility that a tran- 
quilizer is, in fact, a weak psychotogen, and this has very definite implica- 
tions for the method of looking for new tranquilizers. Thank you. 



154 



Effect of Kava in Normal Subjects 
and Patients 

Carl C. Pfeiffer, Henry B. Murphree and Leonide Goldstein 

Section on Neuropharmacology 

New Jersey Institute, Princeton, New Jersey 

Those of you who watched the television news last October saw that the 
Samoans oflFered cups of Kava to President and Mrs. Johnson. The New 
York Times (10-19-65) reported the incident as follows: (1) 

Mrs. Lyndon B. Johnson is the first woman ever offered the royal Kava drink, the 
highest honor Samoan chiefs can bestow on a visitor. She drank it, too. 

Samoans who turned out from every comer of the island to welcome the Johnsons 
yesterday applauded delightedly as the First Lady sipped the bitter juice from a coco- 
nut cup. The President only touched his lips to the cup. 

Later Mrs. Johnson said the drink tasted a little like the milk of coconuts — watered 
down — with a slightly medicinal taste. 

Drinking the brew, made from the pulverized root of the Kava tree, bound Mrs. 
Johnson in fellowship with the chiefs. Both she 'and her husband also made the tradi- 
tional gesture of pouring a bit of the juice on the ground to get rid of evil spirits. 

Subsequently President Johnson, the abstainer, needed two surgical opera- 
tions while Mrs. Johnson's health has remained excellent ! What is in this 
obviously marvelous brew made from the root of the Kava tree? This con- 
ference allows us to review data on Kava gathered in animals and man over 
the period 1954^1962. The data vary in their accuracy from global clinical 
impressions to objective double blind studies using quantitative amplitude 
analysis of the EEG. 

In 1954 we made various extracts of the powdered Kava root and obtained 
brown gums which, while insoluble in water, could be easily suspended in gum 
tragacanth. The alcohol extracted gum appeared to be the most active in mice, 
particularly against strychnine convulsions. 

One of the active ingredients, dihydrokawain, was compared to mephenesin 
and found to be effective but very fleeting in its anti-strychnine effect (2, 3) 
Table 2. The testing in mice was perforce done in the first 30 minutes after 
oral dosing in order to see the characteristic anti-strychnine effect. The very 
short acting drug mephenesin had a comparable effect to that of dihydro- 
kawain. 

Our interest next turned to the two compounds which the Eiker Labora- 
tory Scientists found to be very active in their animal tests {Ji). These were 
dl-methysticin and dl-ethysticin. The methyl congener occurs in Kava while 
the ethyl congener was prepared synthetically. Both compounds are optically 
active so that synthesis provides the racemate while the natural compound is 
an optically active enantiomer. 

We studied in two groups of six normal subjects at the Atlanta Federal 
Penitentiary both dl-ethysticin and dl-methysticin in single oral doses of 



155 



Table 1. — Anticonvulsant effect of Kava Kava in mice 



[All tests at 1 hour after oral dose] 







Metrazol ratio 


Stryehnine ratio 


FT 


PC 


PC 


% Surv. 


Crude Root 


2. 0 gm 


*1. 6 


*1. 6 


2. 1 


50% 


Hot Ale Extr. 


150 mg 


1. 4 


1. 2 


1. 7 


28% 


CH CI3 Ext. 


150 mg 


1. 2 


1. 1 


1. 8 


35% 


Ale. Extr. 


150 mg 


1. 5 


1. 2 


2. 2 


32% 


Control Mice 




1. 0 


1. 0 


1. 0 


0 



FT=first twitch. 
PC=persistent convulsion. 
N = 14 mice/group. 

*Read 1.6 times the control group of mice. 



800 mgm. This dose was chosen because therapeutic trials in epileptics showed 
some degree of seizure control. No significant changes in blood pressure, pulse 
rate, grip strength, hand steadiness, or pupil size occurred. The subjective 
responses were equally divided between stimulant, placebo and sedative re- 
ports. We conclude that these two congeners were not sufficiently active to 
be recognized by our crew of drug sophisticated tasters. 

When the crude root was given to 9 selected, uncontrolled epileptics (6) 
in doses up to 6 grams per day a better degree of seizure control was obtained. 
The same degree of control was provided by an alcoholic extract of the root 
in a dose of 1.0 gm/day. However, continued therapy for several weeks pro- 
duced a lemon tinted skin and sclera which was apparently owing to a chemi- 
cal pigment and is seen characteristically in the Samoans who take Kava 
regularly. Because of this skin reaction the use of root and extract was dis- 
continued in favor of the study of the pure, more active and uncolored prin- 
ciples of the root. 



Table 2. — Anticonvulsant effect of dihydrokawain 









Metrazol 








Dose 


Test 








Strychnine, 






time 








P.C. 








F.T. 


P.C. 






DHDK 


200 


10" 








*1.6 




400 


10" 


1.5 


1 


1 


2.0 




400 


30" 


1.3 


1 


1 






400 


60" 


1.1 


0 


9 


1.1 


Meph. 


200 


10" 








1.2 




400 


10" 








2.0 



Min. Atax. Does=250 mg/kg. 

F.T.=first twitch. 

P.C. = persistent convulsion. 

•Read 1.6 times the control group of mice. 12 mice/group. 



156 



Of the available congeners dl-dihydromethysticin is the most active in 
animals. This compound became available for clinical trial in 1956 as Eiker 
Laboratories #532, and was used in doses up to 1200 mgm/day to control 
epileptic seizures. The anti-epileptic effect was characterized by fewer 
grand mal seizures but no change in petit mal seizure activity. However, 
after one month of continuous therapy some patients showed conjunctival 
and circimaorbital erythema, vomiting and diarrhea. These symptoms were 
considered to be drug induced so that dl-dihydromethysticin was discon- 
tinued. 

Saunders and Kline (6) treated schizophrenics with this drug using 
doses of 800 mgm/day. After 3 months, 14 or 15 patients developed typical 
drug induced skin rashes of the groin and axillae. The reaction disappeared 
10 to 20 days after the drug was stopped, but reappeared when the drug was 
again given to selected patients. The drug had no antipsychotic effect in the 
schizophrenic patients. 

EFG Studies in Normal Vohmteers 

The quantitative EEG technique provides an accurate method to measure 
GNS stimulation, sedation or sleep. Quantitation of the EEG was performed 
with an electronic integrator. This device, the operation of which has been 
fully described elsewhere (7), transforms the complex EEG signals into 
pulses inscribed directly and concomitantly with the direct tracings. The 
number of pulses, for any given time period, is directly proportional to the 
cumulated electrical energy. Calibration is by the application of known 
energy constants. The values obtained therefore can be related to fixed stand- 
ards. The basic time-unit chosen for data analysis was 20 seconds, that is, 2 
pages of standard EEG recording. Thus any 10-minute recording run yielded 
30 successive measurements. 

All the corresponding values from each predrug and postdrug run, as 
obtained from all the subjects involved in each particular study, were aver- 
aged, and mean energy contents (MEC) for the group were thus determined. 
The statistical significance of the changes was ascertained with the t-test. 

Besides these measurements of the level of electrical energy, a careful 
analysis of variability was performed for each time period. We find that this 
parameter of quantitated EEG data is highly informative, not only for the 
detection and characterization of drug effects, but also for baseline features. 
For example, we have found that male schizophrenic patients have much 
less EEG variability than nonpsychotics. In the Tables, the values of the 
standard deviation are computed from the "between subjects, within drug" 
covariance values. Statistical significance of the differences in variability was 
based on F-ratios. For convenience, the covariance levels are expressed as 
the coefficient of variation (CV). Table 3 summarizes our objective findings 
using this technique. 

The subjective reaction of these normal subjects was that the Kava 
principles produced mild sedation or sleepiness. This would be in accord 
with the quantitative EEG findings of the most effective congener, namely 



157 



Table 3. — Quantitative eledroencephalographic studies in normal volunteers given Kava 

type chemicals 



Drug 


Oral 

dose, 
mgm 


N 




C 


Hours following admin. 


1 


2 


3 


4 


5 


6 


Dihydrokawain 


zUU 


r 
0 






105 


101 


99 


112 


117 


114 








yj V 


90 


20 


22 


20 


19 


19 


16 


dl-dihydromethy- 






















sticin 




1 n 




lUU 


99 


103 


110 


104 


101 


105 








O V 




27 


31 


30 


17 


23 


25 


d-dihydromethy- 






















sticin 


1 fin 


1 n 




1 no 


108 


108 


108 


103 


106 


101 








cv 


21 


26 


26 


28 


*39 


*40 


*51 






11 


MEC 


100 


100 


107 


102 


110 


102 


94 








CV 


20 


20 


19 


19 


20 


20 


20 


Meprobamate 


800 


10 


MEC 


100 


96 


*71 


*77 


88 


89 


107 








CV 


19 


*29 


*32 


*38 


*46 


*56 


*39 



•Significant at tlie 1 in 20 level of confidence. 



160 mgm of d-dihydromethysticin. This is evident in the increase in the 
coefficient of variation at the 4, 6 and 6th hours after the oral dose. 

Computer analysis of the EEG after 160 mg of dl-dihydromethysticin 
revealed that there were significant increases in total electrical energy with- 
out significant increases in variability. These increases affected all frequen- 
cies and were maximal two to three hours after dosage. The increases were 
more evident in low-alpha records. When very prominent alpha was present, 
little or no change occurred in total energy or in energy in the alpha band, 
but significant increases occurred in the low frequency portion of the elec- 
troencephalographic spectrum, again without any significant change in varia- 
bility. 

Discussion 

We have found that dihydrokawain is very similar to mephenesin in its 
effect on the strychnine thresholds of mice. Meyer (8) and Meyer and 
Kretzschmar (9) find a close similarity in the pharmacological action of the 
Kavapyrones and mephenesin when tested on the reflexes of guinea pigs. 
The chemical structures are similar in that both can be described as blocking 
compounds of simple oxygen functions. 

If more were known about the physiological deposition of the Kava- 
pyrones a second analogy might be made to the diketone griseofvlvin which 
is also a mild CNS sedative, and is known to exert its antifungal effect by 
deposition in the skin, hair, and nails. This fungicide however is well toler- 
ated by the human skin while the Kava-pyrones are not. If Samoan groups 
can be found who imbibe Kava only during a ceremonial week one would 
expect to find some degree of yellow banding of their finger and toe nails 
if the Kava-pyrones are deposited in keratin. 



158 



CH 

OH OH /=\ P-C^ 
/ ^O-CHg-CH-CHg )>CH2-CH2 

^ ' ^ ' ' 'OCH. 



Mephenesin Dihydrokawain 




0 




Griseofulvin 



Aspirin 



Fig. 1. — The Kava ketopyrones are blocking compounds of three oxygen and a methyl 
functional groups. Other molecules which have a similar sedative effect are griseofulvin 
and aspirin. 



Perhaps the simplest chemical which is a blocking compound containing 
3 oxygens and a methyl functional group is aspirin. This has not been 
studied in animals for its central relaxant action. Quite independently of 
the Kava study we have determined recently the effect of aspirin and other 
mild analgesics on the quantitative EEG of man. Aspirin is the only small 
analgesic which has a typical sedative or antianxiety effect on the human 
brain. One wonders then if aspirin is not a mild type of Kava which has 
been developed in modern society and used without ceremony by the tons 
(as long as the recommended dose on the label does not exceed two tablets) . 



Table 4. — Comparison of meprobamate and buffered aspirin by the quantitative EEG 

technique 



Drug 


Mgm 
dose 


N 




c 


1 


2 


3 


4 


5 


6 


Meprobamate 


800 


10 


MEC 


100 


96 


*71 


*77 


88 


89 


107 








CV 


19 


*29 


*32 


*38 


*46 


*56 


*39 


Placebo 




30 


MEC 


100 


101 


100 


101 


102 


103 


104 








CV 


19 


20 


17 


17 


26 


18 


19 


Buffered asprin 


1000 


20 


MEC 


100 


90 


*83 


*75 


*85 


*85 


*83 








CV 


26 


*37 


*40 


*42 


*39 


*40 


*34 



•Significant at the 1 in 20 level of confidence. 



159 



Conversely one might ask if the Samoans use Kava as a "pain-killer". I 
have been told that the plains Indians have in times past used peyote as a 
pain killing drug. 

We have heard the chemists describe the active Kava-pyrones which can be 
found in the Kava plant. We have studied one minor synthetic modification 
of a Kava principle, namely Ethysticin. We have not had reported today any 
serious attempt to synthesize more coniplex Kava pyrones with more ade- 
quate blocking groups. Thus in dihydrokawain the synthesis of a methylene 
bis compound would be of interest, as also would be a benzohydryl kawain. 
One should keep in mind that as the molecule becomes larger and more effec- 
tive as a blocking moiety, the structure and perhaps the pharmacological 
effect will approach that of dihydrocannabinol another oxygen-containing 
molecule. Also the main physical characteristic of these Kava principles, that 
of poor water solubility and good lipid solubility, will always result in a 
preponderance of pharmacological action on the brain and skin i.e. ectodermal 
tissues. This selectivity should be put to good use in the transport of a prop- 
erly tailored and more active molecule. 

Finally the study of the Samoans and their Kava ceremony remains the 
best and possibly the last area of scientific interest insofar as the intoxicating 
effect of Kava is concerned. 

Summary 

We have studied in animals and man various extracts, extracted chemicals 
and congeners of piper methysticum (Kava Kava). The main pharmaco- 
logical action is like that of central relaxants of the mephenesin-type as shown 
by a specific antagonism to strychnine infusion. Compared to modern syn- 
thetic central relaxants all of the Kava congeners are relatively inactive. The 
most active congener appears to be dihydromethysticin, but this compound 
when given to man in the dosage range of 800 to 1200 mgm daily produces 
side effects and allergic skin reactions. The crude root and extract produces 
a yellowing of the skin similar to that reported in the Kava drinkers of 
Samoa. From the data now available, further study of Kava as a modem 
medicinal agent would not appear to be needed. 

REFERENCES 

(1 ) New York Times October 19, 1966. 

(2) Orloff, M. J., Williams, H. L. and Pfeiffee, O. C. Proc. Soc. Exp. Biol. 70: 25 257 

(1949). Timed Intravenous Infusion of Metrazol and Strychnine for testing anti- 
convulsant drugs. 

(3) JENNEY, E. H. and C. C. Pfeiffer. Annals N.Y. Acad. Sci., 64: 679-89 (1956). The 

Predictable Value of Anticonvulsant Indices. 

(4) Keller, F. and Klohs, M. W. Lloydia 26: 1-15 (1963). A Review of the Chemistry 

and Pharmacology of the Constituents of Piper Methysticum. 

(5) Pfeiffer, C. C. Unpublished data this laboratory. 

(6) Cronheim, G. Report of N. Kline to Riker Labs. 

(7) Pfeiffer, C. C, Goldstein, L., Murphree, H. B. and Jenney, E. H. Arch. Gen. 

Psych. 10 : 446-i53 (1964). Electroencephalographic Assay of Anti-Anxiety Drugs. 



160 



(8) Meter, H. J. Arch. int. Pbarmacodyn. 150: 118-131 (1964). Untersochungen Uber 
Den Antikonvulsiven Wirkungstyp Der Kawa-Pyrone Dihydromethysticin Mit 
Hilf e Chemisch Induzierter Krampf e. 

(5) Meter, H. J. and Kretzschmak. Klin. Woch. 44/15, 902-903, 1966. Kawa-Pyrone eine 
nenartige substansgruppe zentraler Muskelrelaxantien vom Typ des Mephenesins. 



161 



Ethnographical Aspects of Kava 



Clellan S. Ford 

Department of Anthropology, Yale University, New Haven, Connecticut 

The Polynesian term kava is generally used in English to specify the shrub 
Piper methysticum (Forster), its root, and a beverage made from it. With 
slight variation, this is the term used in western Polynesia, including Tonga. 
In Samoa the form is ''ava, in Tahiti ava. In Hawaii it is awa. The Maori 
took with them to New Zealand tales concerning the use of kava but did not 
find the plant in their new home. They found another plant, Piper excelsum, 
which they did not make into a beverage, but which they named kaiodkawa. 
The term kava or its equivalent in Polynesia is also an adjective designating 
various properties of food and drink. In Hawaii it means bitter, sour, sharp, 
pungent. In the Marquesas it signifies bitter, sour, sharp. In Tahiti the range 
is broad, including bitter, sour, acid, acrid, salt, sharp, and pungent 
(Churchill p. 56). 

The use of Piper methysticxmi is not confined to Polynesia. In Micronesia 
it is found in the Caroline Islands. It is found in many places in eastern 
Melanesia: in New Britain, New Ireland, the Admiralties, the Banks and 
Torres Islands, the New Hebrides, and in Fiji. In Melanesia its use is of spotty 
distribution. In some instances islands only a few miles apart dilffer from 
one another in regard to the use of kava. For example the people of Ambrym 
in the New Hebrides look down upon their neighbors on Pentecost Island, 
only seven miles away, because they drink the beverage. Sometimes, as in the 
case of Tikopia (a Polynesian outlyer in Melanesia), betel chewing and kava 
are found together. On Tikopia, interestingly enough, the beverage is not 
drunk but is poured on the ground as a libation to the gods. 

Since our personal experience with kava and its uses is for the most part 
confined to Fiji and Tonga, the remainder of this discussion will relate to 
those islands. My wife and I have visited most of the major islands in Tonga, 
the islands of central and southern Lau, the Yasawas, Kandavu, Taveuni, 
Ovalau, and a number of villages on Viti Levu and on Vanua Levu. In 
practically all of these places we have participated in kava ceremonies of 
one sort or another, and I must admit that this has been an enjoyable 
experience. 

The Fijian term for the plant, the root, and the beverage made from it is 
Yaqona. This term is apparently without parallel outside the archipelago, 
in either Melanesia or Polynesia. The word does not appear to be used in an 
adjectival form. Lester, however, reports that a word Qona is used on the 
northwest coast of Viti Levu to denote both "beverage" and "bitter." He 
suggests that this may indicate that it was to this part of Fiji that kava was 
first brought and that these were the people who supplied the name Yaqona, 
which is now universally used throughout the archipelago. More commonly 
in Fiji "bitter" is gaga^ which also means '■'■poisonous.'''' 



162 



Our first introduction to kava was on the island of Naviti in the Yasawas 
off the northwest coast of Viti Levu. We had been taken there by a small 
copra vessel and dropped off on the reef in the early hours of the morning. 
We were met by a number of Fijians who carried us and our luggage ashore 
and who escorted us to the house of Koko, Katu Filimone Kama, in the 
village of Kese. 

It was, for us, an awkward situation. The Fijians on the island of Naviti 
had an English vocabulary of scarcely more than "quite," "rather," and 
"hello," and our Fijian was nil. We were in age approximately twenty-five 
and quite unaccustomed to the South Pacific. Of course we had read a good 
bit about the Fiji Islands and the indigenous customs, including kava drink- 
ing. We had, for example, been able to read about kava in the Encyclopaedia 
Britannica — you can still read it there — and I quote : 

KAVA ... an intoxicating, but non alcoholic beverage, produced principally in the 
islands of the south Pacific, from the roots of leaves of a variety of the pepper plant 
{Piper latifoliuni or P. methpsticum) . The preparation is peculiar. The roots or leaves 
are first chewed by young girls or boys, care being taken that only those possessing sound 
teeth and excellent general health shall take part in this operation. The chewed material 
is then placed in a bowl, and water or coco-nut milk is poured over it, the whole is well 
stirred, and subsequently the woody matter is removed by an ingenious but simple 
mechanical manipulation. The resulting liquid, which has a muddy or cafe-au-lait ap- 
pearance or is of a greenish hue if made from leaves, is now ready for consumption. The 
taste of the liquid is at first sweet, and then pungent and acrid. The usual dose corre- 
sponds to about two mouthfuls of the root. Intoxication (but this apparently only applies 
to those not inured to the use of the liquor) follows in about 20 minutes. The drunkenness 
produced by kava is of a melancholy, silent and drowsy character. Excessive drinking is 
said to lead to skin and other diseases, but per contra many medicinal virtues are ascribed 
to the preparation. . . . [Anonymous]. 

We also had read various colorful reports about kava and its use written by 
earlier visitors to Fiji, as in the following examples : 

In their devotion they have a kind of sacrament, using the root called on the Sandwich 
islands ava, but angooner in this country. In the first place they wash the root clean, 
and then chew it, and put it into a large plantain leaf, which is as big as a small tea table, 
which they lay in a hole in the ground, and then pour a small quantity of water to it, and 
rinse the substance out. This liquor the Rombetty serves out in small plantain leaves to 
his people, and as each one receives it, they all clap their hands and say mannor angooner, 
which is returning thanks to God in their way. After partaking of this they think they are 
bappy, its effect being similar to that of laudanum [Patterson p. 90] . 

The great token of hospitality, when one enters a native house, and especially that of 
a chief, is the preparing and presenting to the guests the native drink, called kava, an 
article never lacking in tlpUng Fiji, as we were often convinced, to our sorrow. So we 
are not surprised that Patioli should call for kava the moment the conversation waned. 
In Samoa it is considered very rude to refuse to drink the beverage, but that is a punish- 
ment we can hardly Inflict upon ourselves ; so we will allow some pressing engagement to 
call us away. . . . Kava has medicinal qualities of not a little power. Drunk to excess, 
it acts like opium, and the habit once formed cannot easily be broken. There are white 
men, on some of the islands in the South Seas, who live almost entirely upon the baleful 
preparation. To them it is as much a necessity as is the morning dram to an inebriate in 
other lands. To the Inexperienced, the very thought of drinking the stuff is repelling, but 
if he can summon courage to try it, he will find a cup of it refreshing and somewhat 
nutritive. The natives very justly attribute some of their ailments to an inordinate use of 



163 



it. The liabitual kara drinker may be recognized by bis fishy-looking eyes and the scaly 
appearance of his skin [Adams pp. 117-20] . 

I had tasted it on several occasions, this kava of the other islands, without enjoyment. 
But I recalled a warning from several old-timers I had met that one could not more 
grievously offend a Fijian than by refusing this beverage, whose serving is everywhere 
such a ceremonial, prescribed by such rigid custom. . . . "Will this go to my head?" I 
asked Sakobi, remembering the waiting boat- 

•'Xo. Xo go to head," he assured me. And Jcava, as a matter of fact, is not an alcoholic 
intoxicant. Rather it might be described as a mildly stimulating drug. A brownish 
murky fluid, slightly pungent and acrid, it is usually obnoxious to the novice, 
but Europeans in the islands often acquire a taste for it, and business men 
frequently keep it in the ofiBce for an occasional swig with their customers. Its 
constant and immoderate use over a long period of years is sometimes injurious 
to the eyes, so that old /i-ara-topers often become nearly blind, but taken moder- 
ately or even in large quantity from time to time it is of acknowledged medicinal value, 
to such extent that the most zealous missionaries do not combat the native custom. And. 
not being an intoxicant, it does not go to one's head ; one can drink any amoimt of it and 
remain clear minded. The funny thing about it, however, is that it does go to one's legs. 
Sakobi, answering my query literally, had neglected to tell me this. But I discovered it 
for myself when, bidding my hosts adieu at midnight, I felt my knees wobble and slid 
like a fireman down the slippery pole that led across the moat. At the moment, I at- 
tributed the mishap to the stiffness resultant from sitting cross-legged all evening in an 
unaccustomed posture. But when we started out across the maze of roads and tracks 
toward the wharf, where the skipper was conscientiously sounding the promised fog-horn 
as a summons to hasten, there was no question but that something was wrong with the 
legs themselves. 

"Come here, Sakobi. Give me a hand." 

He locked his arm through mine. But his legs were just as bad. For a quarter-mile we 
made progress, leaning against each other as our feet gravitated toward the center. Then, 
despite all efforts at control, his started for the left and mine for the right, and we both 
sat down heavily [Foster pp. 238-^] . 

These and many of the other early missionary and travel reports were 
equally disturbing, and it was with no little apprehension that we sat in the 
Roko's hut wliile the Yaqona was being prepared for our welcome reception. 
To our relief, the root had been pulverized with a mortar and pestle rather 
than chewed. But there were other sources of concern. We had been schooled 
to beware of water unless it had been boiled. And here was a stalwart Fijian 
plunging his brown hands and wrists into a wooden bowl to knead the mix- 
ture while another poured water over the powdered root. "What risks were 
we taking : drunkemiess, disease, polluted water, unclean hands ? The boat 
had left, not to return for six months, and there was no other way off the 
island, not even by outrigger. And the only medical assistance on the island 
was said to be a Fijian "doctor" with one year's training in first aid. To 
drink or not to drink was the question. 

We had been told by Europeans in Suva that it was imperative that we 
accept what we were offered, including kava, when we were in a Fijian 
village. Furthermore, we had been told that the brew was not as bad as it 
was made out to be and that the best thing to do was to drink it down 
rapidly — that if we sipped it we Avould be lost and never finish the cupful, 
which would be really bad mannered of us. So when the cupbearer, glistening 
with coconut oil, brought a cupful to me and then to my wife we downed 
it without hesitation. To me it tasted like the smell of a cedar lead pencil 



164 



when it is sharpened, and aside from a slight numbing sensation at the base 
of the tongue and in the throat, there was nothing out of the ordinary about 
the experience. In fact when we struck lights to our cigarettes after having 
had our first taste of kava, they seemed to be especially satisfying. 

During the year that we spent in Fiji on that field trip in 1935-36 we 
drank a great deal of kava, probably as much if not more than many of the 
Fijians. We became quite fond of it and never experienced, insofar as we 
could detect, any of the ill effects attributed to the drink. Nor did we ever, 
during that trip or subsequent shorter trips to the islands of the South 
Pacific, see a native "drunk" from kava drinking. Exhausted, yes. Some of 
the all-night three- and four-day-long festivities that we attended could 
not fail to wear people out, but I am convinced that the kava did little to 
cause what could more accurately be described as a state of being "punch- 
drunk" with fatigue. 

Apparently the early inhabitants of Fiji brought the kava plant with 
them from Indonesia. From Fiji it was probably introduced somewhat 
later to Tonga and to Samoa. In Fiji, as far as can be determined it appears 
that the root was originally grated on mushroom coral or pounded with 
stones before it was mixed with water to prepare the beverage. The practice 
of chewing {mama) the root seems to have been introduced to Fiji by 
Tongans or Samoans, although there is a possibility that it may have come 
to them from other parts of Melanesia. The custom of chewing kava was 
observed by early travelers and missionaries in the eastern islands of Lau 
and in the coastal settlements on Viti Levu. Young men chewed the root and 
deposited it in a bowl to form the basis of the kava mixture. But chewing 
the root was never practiced in much of the interior of Viti Levu or Vanua 
Levu. The church and the government discouraged the practice, and today 
the root is either brayed between two stones or pulverized in a wooden 
mortar with a pestle. An oft-repeated story justifying the discouragement 
of chewing kava as a method of preparation relates that in the 1870s a Dr. 
Macgregor weighed six ounces of the root, which was then chewed in the 
usual manner. When deposited in the bowl it weighed seventeen ounces 
(Gordon-Cumming p. 51) . 

There is some evidence to indicate that the beverage was at one time 
prepared in an earthen pit lined with leaves, constructed much like an earth 
oven. The development of pottery in Fiji took place quite early, however, 
and pottery bowls took precedence and were used in many parts of the 
islands for kava mixing. Very crude wooden bowls resembling the pottery 
ones were used elsewhere. At least four to five hundred years ago the modern 
wooden bowls came into general use and for the most part replaced the 
pottery bowls. As far as is known, these wooden bowls were made only on 
Kambara in Lau, and were thence disseminated to the rest of Fiji and to 
Tonga. Whether the design for the bowl originated in Kambara or was 
introduced thare from Samoa and/or Tonga is not known, but since the 
term by which the bowl is known in Fiji, tanoa^ is a Polynesian word, it 
seems likely that the bowls are of Polynesian origin. In any case, the tanoa 
has been in use throughout most of Fiji for the past few centuries. 



165 



The kava bowl varies in size and shape, but it is generally round, from 
one to three feet in diameter, and with four legs (occasionally more) all 
made from one piece of wood, vesi (Afselia Mjuga). The front of the bowl 
has a triangular suspension lug with two holes, to which sennit braid is at- 
tached to provide a means of hanging the bowl on the wall. Today all chiefly 
kava bowls have white cowrie shells attached to the end of the cord. The lug 
and its attached braid are important parts of the kava bowl and play a major 
role in the kava ceremonial, as will be described below. The tanoa is never 
used for any other purpose than that of mixing kava, and after a long 
period of use its interior surface collects a blue-green patina. 

The most usual cups for serving kava are the pointed halves of coconut 
shells, scraped thin and highly polished. Most cups are about two inches in 
diameter, but some are much larger. We have one that was presented to me 
which measures six inches across and holds well over two cupfuls of liquid. 
It is very old and, like the older kava bowls, it has an interior patina. 

When the time comes for the kava to be mixed, the pounded or grated root 
is placed in the bowl. To this is added water, which is kneaded together with 
the powdered root. More water is added and the mixing progresses. A strainer 
of vau (hibiscus fiber) is used at the end of the mixing to strain out the 
woody particles from the drink. As the strainer collects fibers, it is wrung 
out and taken out of the bowl so that the particles can be shaken out. This 
process is repeated several times until the liquid is relatively clear. If the 
mixture appears to be too concentrated, more water is added. Then the kava 
is ready for serving. 

It is believed that the kava ceremony in Fiji was formerly a predominately 
religious rite, carried out by priests. The purpose was to establish communion 
with the supernatural. Through the kava ceremony the priests were believed 
to reach the gods and ensure their assistance in life here and hereafter, 
Eivalry existed between these religious leaders and the political leaders. 
As the latter grew in strength by virtue of consolidating more and more 
territory under their control, they ousted the priestly class from their posi- 
tion of power, Coincidentally, the missionaries came in to take over the all- 
important function of cementing the relationship between the people and 
the supernatural. The political leaders took over the kava ceremony, and 
from that time on it has been more socio-political than religious, though 
much of the ritual can be traced back to usages in the past that were strictly 
religious in character. This change in emphasis apparently occurred early 
in the eighteenth century, and the formal kava ceremony has remained much 
the same ever since. 

In placing the current kava ceremony in perspective it is important to 
note that Fijian and Tongan society was and still is highly conscious of 
differences in rank or status. Persons are arranged according to inheritance 
in a hierarchy from kings to high chiefs, to lesser chiefs, and to commoners. 
One of the major functions of the kava ceremony is clearly to reaffirm (or 
establish) status. When visiting dignitaries arrive, this is the means by which 
strangers are accorded their position in the village or district to which they 
have come. Among a people whose inter-island and inter-district relationships 



166 



were more often than not of a warlike nature, this was a respected medium 
through which rapport could be established, at least a temporary truce 
declared, and a modicum of trade relations ensured. 

Formal kava ceremonies, yaqona vakaturaga, are imbedded in a large 
complex of activities. Much has to be done in preparation, for many days 
in advance, Wlien the participants have gathered and are properly seated, 
the ceremony begins with the formal presentation of offerings : kava roots, 
whales' teeth,^ tobacco, food, and articles such as pandanus mats and tapa 
cloth. Then comes the kava mixing and drinking. After this solemnity there 
may be dances and songs. In any case there follows, perhaps an hour or 
two later, the distribution of the feast foods and all those assembled proceed 
to eat. 

The seating of the participants during the presentation of offerings and 
the kava ceremony is most important. The kava bowl is located in the middle 
of the meeting place. Behind it is seated the kava mixer. At his side, both to 
the right and the left are what might be termed helpers. Behind the kava 
mixer and the bowl are seated a number of men who will form the chorus 
for the chanting which accompanies various parts of the ritual. The wa ni 
tanoa, the sennit braid with its white cowries, is stretched out directly away' 
from the mixer pointing toward the most important personage present, the 
chief of the district or a visiting dignitary. The first cup of kava will be 
presented to him. To his left and slightly forward sits his talking chief. To 
his right sit a selected number of lesser chiefs, all slightly forward toward 
the bowl. 

The significance in Tonga of the suspensary lug and its cord has been 
vividly described by Sir Peter Buck, himself part Polynesian (Maori) : 

The following incident illustrates the method of indirection dearly loved by the 
Polynesians. After the death of the last Tui Tonga, two of the greatest supporting 
chiefs of the Tui Tonga dynasty came to George Tuhou, who had been gathering the 
reins of temporal power into his hands, and informed him that they wished to make 
kava for him. They conducted him into the guest house and, seating themselves behind 
the kava bowl, proceeded to prepare the kava. George Tubou sat down opposite and 
waited. He looked casually across at his companions and saw what must have been a 
soul-stirring sight. The suspensory lug of the bowl was pointing at him. The chiefs 
had not spoken, but the speechless bowl was announcing a king [Buck p. 299]. 

The precise seating arrangement and the form of the ceremonial differs 
slightly from one island and district to another, and there is no need to 
describe these in detail here. 

However, it may be useful to attempt a generalized description so that 
some picture of such an occasion is before us. Imagine then, the chiefs sitting 

1 The tabua, or whale's tooth, is the ceremonial currency of Fiji. Holes are bored in each end 
of the tooth, to which is attached a cord of sennit braid or pandanus. A proper cord is made of 
four-ply braid, known as sui ni gata or "bones of the snake." Interestingly enough, the tabua is 
not just a whale's tooth ; it must be old, oiled and polished, and it must have an acceptable cord. 
What was employed in its place before whales' teeth were available is not known. Stones shaped 
much like whales' teeth have been found dating back to early times. Wooden tabuas have been 
known to be used. A suggestion has been made that originally the human collar bone was used. 
Be this as it may, for many generations the tabua has been the most important possession of any 
Fijian, and generally speaking they are predominantly in the custody of high ranking chieftains. 
With the presentation of a tabua at a proper kava ceremony, one may obtain from a chief almost 
anything one is desirous of having. 

167 



facing the 'bowl and the proceedings about to begin. The occasion is that of a 
visiting chief from, another village. All of the actual participants are in 
colorful costume: some with yellow pandanus kilts, some with green leaf 
sulus^ some garbed with colorful tapa, the native bark cloth. All are glistening 
with coconut oil. 

On both sides, at a short distance away from the circle of those participat- 
ing, may be several hundred men, women, and children — observers only. Sud- 
denly there is a hush of voices, and then complete silence. From this point 
on none of the participants, seated cross-legged in fixed position, will make 
any movement that is not a part of the prescribed ritual. There is no talking, 
no smoking, no uncrossing of the legs, no extraneous movements of the arms 
or head. All attention is focused on those who are performing their roles in 
accordance with traditional rules. 

The visit ing chief moves into the center of the circle, crawling on his knees. 
He carries with him in his hands the root of the kava plant, or perhaps a 
tabua. Now comes the presentation: ai sevu sevu. With cupped hands he 
claps three times and addresses the host chief. He says then in effect "here 
is a small offering ..." Tlie host's talking chief, or master of ceremonies 
and the chief himself interrupt to say "a great thing, a great thing," and an 
interchange of deprecatory remarks on the part of the visitor folloAved by 
complimentary comments by the host continues for a short time. Finally 
the master of ceremonies says "let it be presented." At this point the partici- 
pants clap their hands in unison. 

The master of ceremonies, with his hands lightly resting on the offering, 
announces in stylized form the acceptance. This concluded, the kava mixer 
tilts the bowl toward the host chief, to show him that the powdered root is 
ready. In response, the master of ceremonies says "Zc>m&(x" which means 
"proceed to mix." An attendant pours water in the bowl and the kneading 
process takes place. After several minutes the kava mixer holds the strainer 
above the bowl, allowing some of the beverage to pour into it. If the master 
of ceremonies thinks the drink is too strong he calls out in effect "More 
water!" Water is added and the procedure repeated until the master of 
ceremonies, satisfied, says "Enough water, strain it." At this point the men 
behind the bowl begin to chant, and this will continue until the kava is served 
to the chief. 

When the kava maker considers the beverage properly strained he strikes 
a pose with hands together and, looking into the bowl, murmurs that "the 
kava is ready to be served." Hearing this, the master of ceremonies says 
loudly '■^Cobo — i.e. Clap," whereupon the kava mixer and his attendants, one 
on either side of him, clap with cupped hands three times. The cupbearer, 
whose face is usually blackened and whose arms and legs bear circlets of 
leaves, appears at the bowl. The kava mixer lifts his strainer and allows the 
beverage to trickle into the cup which the cupbearer holds out for him. In 
time with the chanting the cupbearer, now partly upright with knees bent, 
sways and moves forward in graceful movements until he is quite near the 
chief. At this point the chanting stops. The cupbearer crouches down low, 
holding his cupful of kava in both hands with arms outstretched toward the 



168 



chief. The master of ceremonies says "Go ahead, rise up" and the cupbearer 
stands up and walks to the chief, to whom he gives the cup of kava. The 
chief now drinks the kava. As soon as the master of ceremonies sees that 
the chief has finished drinking (in some^ instances the chief may spin the 
empty bowl in the center of the mat) he signals again for the participants 
to clap three times. 

The master of ceremonies receives a cup of kava from the cupbearer, and 
perhaps the visiting chief and his talking chief. This ends the formal part 
of the ceremony, and this is announced by the master of ceremonies who 
proclaims that the "chiefly kava is dry." The wa ni tanoa is pulled back out 
of sight. The kava mixer and his attendants clap three times. From then on 
the formalities are slackened. It is now permissible to talk and to smoke 
while the other chiefs are being served their kava. This may last from one 
half hour to more than two hours, until the bowl is emptied. Never is a kava 
bowl left containing unused beverage. Following this comes the division of 
feast foods and then the feast itself. 

Good descriptive accounts much more elaborate than the sketch provided 
above are available in the literature (cf. Hocart, Lester, and Mariner). The 
important things to note here are, first, that throughout the entire proceed- 
ing the arrangement of participants and their behavior, including the chant- 
ing and the movements of the cupbearer who serves the kava, are rigidly 
prescribed by custom and, second, that the occasion is a very solemn affair. 
In the not-too-distant past, the entire village was compelled to be silent while 
kava was being prepared in formal fashion, and if anyone, even a child, 
made any noticeable noise, he was clubbed. We have a recording of a formal 
kava ceremony held at Naviti in the Yasawas in 1960 that was performed 
especially for the purpose of getting it on record. The tape recorded the 
ceremony clearly, and despite the fact that there was an audience of more 
than two hundred men, women, and children, no noise extraneous to the 
performance is to be heard except for the occasional cackling and crowing 
of the native fowl. 

Apart from the Yaqona vakaturaga^ the formal kava ceremony with which 
we have been concerned, kava drinking takes place in Fiji quite infor- 
mally. It is frequently drunk in casual fashion by all inhabitants, including 
Europeans. Children do not drink kava, and at what age they begin to 
participate is difficult to determine. In native schools they are taught the 
ceremonial, using plain water as a substitute for kava and wooden tabuas. 
In Suva, kava is available in most stores and shops for the customer who 
wishes a cup. A large bowl of kava is always available at the Tourist 
Bureau, Avhere, to please American tourists, there is usually a lump of ice 
floating in the drink to keep it cool — to my taste, definitely not an im- 
provement. Among the Fijians, kava seems to be holding its own against 
the importation of alcoholic beverages and soft drinks. An interesting story 
concerning Ratu Sekuna relates that upon going to Oxford for his LL.D., 
he was concerned that he would not find kava there. So he had many bowls 
prepared, placed them in the sun, and took with him to Oxford the residue, 



262-016 0-67— 13 



169 



"instant kava," which he could then simply mix with water when he 
desired. 

It is clear that after one gets used to its peculiar odor and flavor, kava 
does provide a pleasurable sensation. Added to this fact is the long tradi- 
tion of kava drinking as a part of a large and important complex of 
activities, including gift exchange, chanting, dancing, and feasting. 
Drinking kava is considered appropriate to a wide variety of occasions, 
from birth through marriage and death. It is the only chiefly way to wel- 
come an important visitor. Sharing a bowl of kava tends to foster socializ- 
ing and friendship, and to the Fijian it is unthinkable that kava should 
not be a part of commemorating any important event. Kava is never, to 
my knowledge, drunk alone. The practice is solidly imbedded in social and 
political context. 

The complex of the customs surrounding kava, which has been briefly 
described above, is unique to those islands in the South Pacific where it 
has been traditional for generations. It is impossible to find precise paral- 
lels in other parts of the world. On the other hand, if one concentrates 
upon one particular aspect of the complex at a time, it is possible to ex- 
amine somewhat similar phenomena for comparative purposes. It is im- 
portant to remember, however, that such parallels as may exist in other 
parts of the Avorld rarely imply any direct historical connection. 

If one singles out the practice of chewing the root as a method of 
preparing the beverage, which was widely practiced in western Polynesia, 
one can find many parallels elsewhere. Throughout southern Asia there 
are customs of premasticating rice or other grains to produce fermented 
drinks or wines. South American cMcha. a fermented drink, is prepared 
in similar fashion from premasticated maize or sweet cassava. Despite the 
similarity between the preparation of these fermented drinks and the 
method of preparing kava in some parts of the South Pacific, there seems 
to be little justification for going further than to point out that premastica- 
tion has its uses as a means of producing chemical changes in the substances 
chewed. And the premastication of food by mothers to feed their infants 
is such a universal custom that the probability of independent inventions 
using this method for the preparation of beverages is extremely high. 
There certainly does not appear to be any support for the notion, implied 
by Ling Shun-sheng (pp. 84-86), for example, that there is a specific 
historical connection between the practice of premasticating grains for 
fermented beverages in Asia and in South America and the chewing of 
kava in the South Pacific. 

If one concentrates on kava itself, no direct equivalent is available. But 
a related plant. Piper hetel, is used throughout a wide area to the west of 
the kava drinkers, including western Melanesia, Indonesia, Formosa, and 
much of Asia. In these areas, people chew a mixture of betel leaf or seed 
together with lime and the nut of the areca or other palm tree. The effects 
of chewing this mixture are said to be much like drinking kava, only more 
so. Betel chewing has its social connotations, and in many places, sharing 
the betel mixture, either before or after mastication, plays an important 



170 



role in establishing friendships, in courtship, and in marriage. But there 
the resemblance to the kava complex comes to an end. 

As to other aspects of the kava ceremonial and its associated practices, 
there are many parallels elsewhere and many of these it might be interest- 
ing to examine, but it does not seem appropriate to do so here. For example, 
the attention paid to the precise seating arrangements has much in common 
with formalized gatherings in most societies that are conscious of status 
differences, including official dinners in Washingon, D.C. The sharing of 
food and drink as a means of declaring a temporary truce or ensuring 
protection through the establishment of a mutual bond has many parallels, 
extending from "breaking bread" to the establishment of "blood brother- 
hood." In its religious aspects, some of the rituals associated with kava 
drinking have parallels that come readily to mind, including certain 
aspects of Christian ritual. 

Although certain aspects of the complex may be related functionally 
to practices in other parts of the world, it is clear that the kava ceremony 
and its associated practices as known in the South Pacific have become an 
institution which is unique in the part it plays in the life of the people. 

There still remains the basic question: To what can the all-pervasive 
role of kava be attributed ? Is it due to the physiological effects of the bever- 
age itself? Are these so powerful that they in a sense demand recognition 
and that from this flows the development of the involved social, political, 
and ceremonial practices which surround its usage? Are the accounts of 
early travelers and missionaries to be trusted? If so, how is their evidence 
to be reconciled with our experiences ? 

It has been suggested that the accounts of the effects of drinking kava 
are simply erroneous fabrications by the early missionaries, which have 
been perpetuated throughout the decades (Churchill pp. 57-59). In this 
connection it is interesting to note that some of the early descriptive phrases 
continue to be repeated verbatim in later accounts, usually without any 
reference to an earlier source. At the same time, it is difficult to dismiss 
without consideration personal experiences reported by a trained observer, 
such as that related by Hocart (p. 59), who writes: 

The intoxication caused by kava is called mateni, meaning death from or illness 
from. The expression mate ni ytmggona is also used. To recover is mbula (to live). 
This intoxication dulls the countenance. As I experienced it, it gives a pleasant, 
warm, and cheerful, but lazy feeling, sociable, though not hilarious or loquacious; 
the reason is not obscured. In time a certain dullness settles on the company, in 
which the kava and the late hour probably both have a part. Once after heavy 
drinking I felt miserable and found it diflScult to walk straight; on turning into 
bed, I felt sick and could not get to sleep. Such intoxication is rare because in Lau 
the kava is so diluted and served in such small cups that many rounds can be 
drunk with impunity. Habitual drinkers are said to become intoxicated more quickly 
than occasional ones. Kava has no unpleasant reaction next morning, other than 
indolence and lack of appetite. Habitual drinkers can be noted by their watery and 
bleary eyes, their dull skins, which in bad cases become scaly. 

On the other hand it will be noted that the latter part of his statement 
carries the usual description of the effects of drinking kava without any 
substantiation from personal experience. His illness might easily have 



171 



been from some other cause, since he does not indicate that on other 
occasions he was similarly affected. 

One matter which has not been stressed but which might conceivably 
be important is that social kava drinking commonly takes place inside of 
a hure, or native house. The drinking may last for hours. During this time 
quantities of strong native tobacco are smoked. And if the doors are closed, 
as is the case in relatively cool weather, the atmosphere can become pretty 
thick with smoke. Several times this happened to us and the effects were 
not pleasant. The atmosphere, coupled with sitting cross-legged for such a 
long time, can easily produce some unsteadiness which, I suppose, could be 
attributed to the drinking of kava if one were predisposed to think so. 

Of course it is possible that the experiences we have had are not com- 
parable to those of earlier times. The drink may have been much stronger 
than that which we have been accustomed to. Kava prepared by pre- 
mastication, which we have never had, may, through the action of saliva, 
have quite different properties. However, those who have drunk both re- 
mark merely that kava prepared by premastication is a smoother and more 
pleasant drink than that prepared by pounding and grating. 

With the evidence available, it seems that early reports on the phys- 
iological effects of kava drinking were greatly exaggerated. That kava 
does have some rather noticeable reactions, including the slight numbing 
of the tongue and throat, is clear, and it is certain also that a desire for 
the odor, taste, and sensation provided by drinking kava can be acquired. 
But this seems hardly sufficient by itself to account for the part which kava 
plays in the socio-political and ceremonial life of the people. 

It seems more likely that in considerable measure the importance of kava 
to the people of western Polynesia and Fiji is derived from the part it 
plays in their life rather than frojm whatever physiological effects it may 
have. Kava has become the focus of importance in so much of their life- 
time activities that they have come to treasure it far more than seems 
warranted by its intrinsic properties. Kava drinking has become part of 
the traditional way of life. As the Fijian puts it kava is vaka viti — 
Fijian custom. 

REFERENCES 

Adams, Emma H. "Jottings from the Pacific. Life and incidents in the Fijian and 
Samoan islands." Oakland, Pacific Press Publishing Company, 1890. 

Anonymous. "KAVA (Cava or Ava)." Encyclopaedia Britannica 13 : 299. Chicago, 
Encyclopaedia Britannica, Inc., 1944. 

Buck, Peter H. "Vikings of the sunrise." New York, Frederick A. Stokes Company, 1938. 

Churchill, William. "Samoan kava custom." Holmes Anniversary Volume, pp. 56-66. 
Washington, 1916. 

Foster, Harkt L. "A vagabond in Fiji." New York, Dodd, Mead and Company, 1927. 
GoRDON^UMMiNG, CONSTANCE Frederica. "At homc in Fiji." New York, A. C. Armstrong 
and Son, 1882. 

HooART, Arthur Maurice. "Lau Islands, Fiji." Bernice P. Bishop Museum Bulletin 62. 
Honolulu, 1929. 

Lester, R. H. "Kava drinking in Vitilevu, Fiji." Oceania 12 : 97-121, 226-254, 1941-1942. 
Ling Shun-sheng. "A comparative study of kava-drinking in the Pacific regions (sum- 
mary)." Bulletin of the Institute of Ethnology, Academia Sinica 5 : 77-96, 1958. 



172 



Mariner, William. "An account of the natives of the Tonga Islands, in the South Pacific 
Ocean." Compiled and arranged from the extensive communications of Mr. William 
Mariner, several years resident in the islands. By John Martin. 2 vols. London, printed 
for the author, 1817. 

Patterson, Samuel. Narrative of the adventures and sufferings of Samuel Patterson. 
Compiled by Ezekiel Terry. Palmer, Mass., from the press in Palmer, 1817. 



173 



Discussion 



Chairman — Georg E. Cronheim 
Members of the Panel — JOSEPH P. Buckley 

Clellan S. Ford 
Carleton Gajdusek 
Lowell D. Holmes 
Murle W. Klohs 
Hans J. Meyer 
Carl C. Pfeiffer 

Chairman Dr. Cronheim : Perhaps we can start with some of the written 
questions. I also want to make it plain that if any participant wants to ask 
a question of, please feel free to do so. 

Here is a question that we may direct to either Dr. Holmes or Dr. Ford, 
or to both of them, and it reads as follows : "Several of the speakers have 
stated that, while Kava drinking produces ataxia and physical weakness, 
it leaves the intellect clear. Is there any corroboration for this other than 
introspective reports?" 

Dr. Holmes : I might start with this. I would point out that much of the 
analysis of Kava drinking that I have done has been after the fact. In other 
words, this symposium came into view about two and a half years ago, and 
by that time I had already made a study of Kava drinking. It is one of the 
foremost institutions found in the area, and you can't help but notice it and 
write down all of the details, but I don't have any quantitative data. 

I do have a few ideas that might relate to this : For example, the drinking 
of Kava by the young men very frequently is followed by very active dancing. 
It is a very energetic and physical sort of dancing, and if there were any 
problems with the legs I doubt if they could do it, because a lot of time it 
involves going down very slowly, that is to say, bending the knees very 
slowly until they almost touch the ground, and then raising up again. If 
there were any muscular problems, I doubt if they could do this sort of 
thing. 

As far as keeping the intellect clear, I can recall one occasion when I Avas in 
the islands by myself — my wife was on another island teaching nurses. I found 
things kind of boring, having nobody to talk to for a portion of the day. 
I would have the boys prepare Kava, and I would sit there and work up my 
notes and drink Kava constantly. 

I will admit I didn't get up very much. I was sitting there typing, but I 
was thinking and reasoning out certain things that I had observed, and as 
far as I am concerned, I did not experience any curtailment of intellectual 
abilities, nor did I experience any emotional problems. 

Dr. Ford: I might just add one observation. In Fiji they have meetings 
of the men who sit around and discuss what the day's activities are going to 
be, and what their long term, maybe two or three activities are going to be, 



174 



such as the building of a house, going on a fishing expedition, or whatever it 
might be. These meetings are invariably accompanied by a good deal of 
Kava drinking. It seemed to me that the Fijians were much sharper in their 
decisions and thoughts how to proceed while they were having Kava, than 
during other casual conversations. 

I never noticed that drinking Kava made the men dull. If it were anything 
it would be the reverse ; they would be more aware of what was going on after 
having had Kava than before. 

Chairman Dr. Cronheim : Maybe we can turn to a question on a com- 
pletely different aspect. Here is a question directed to Dr. Pf eiffer : "Will 
you please describe the effect of alcohol on the mean energy content and coef- 
ficient of variance, and compare these effects with those of Kava Kava?" 

Dr. Pfeiffer: The effect of alcohol in a relatviely low dose, that of an 
ounce and a half of bourbon, or similarly diluted laboratory alcohol, is that 
of an anti-anxiety drug, meaning a depression in mean energy content and 
an increase in variability. 

I would like to add that in the early days of mephenesin testing we had a 
ten percent suspension of mephenesin; this could be ingested at about the 
teaspoonful level and produce everything that has been described as hap- 
pening with Kava. I wonder if there is any emulsifying agent in the natural 
Kava that would suspend some of the substances that we consider not water 
soluble but which have a definite effect ? 

Chairman Dr. Cronheim : Does anybody Avant to comment on this last 
question from Dr. Pfeiffer? 

Mr. Klohs : I would suspect in regard to the compounds we worked with, 
the d-pyrones, where water solubility is negligible, that mastication may 
result in a sort of an emulsion being formed where the particles are sus- 
pended in the water, and in that way you could get some of the physiological 
effects. That is the only thing that I could suggest. 

Dr. Ford : The Kava is stirred before each cup is provided. 

Mr. Klohs : You would get suspended material here. 

Chairman Dr. Cronheim: I have a question here for Dr. Gajdusek: 
"What is the cargo cult," you spoke of ? 

Dr. Gajdusek: Cargo cults form the subject of detailed studies by pro- 
fessional anthropologists for each area in New Guinea or the Islands. In 
the particular cult on Tanna, there was a gradual disenchantment of the 
people on the Island with the European planters, and the missionary people. 
There was a turning back to traditional ceremonies and the traditional way 
of life, with the addition of many of new features taken from the missionary 
teaching but re- interpreted in the way the people themselves wanted to inter- 
pret them. 

This was definitely associated with a request that all Europeans leave the 
Island and that the Government not bother them. A great deal of mythology 
sprang up around it. There is a whole French book on it, published in Paris, 
devoted to the cults and myths associated with this movement, or "cargocult". 

Kava came into the matter in that it became a part of the whole cult. Women 
and children occasionally drank, but all of the adult males were drinking a 



175 



great deal of Kava made from the fresh root. It is only on Tanna that a fully 
fledged cargo cult of that sort has developed in the New Hebrides. 

Tongariki, where the observations I was reporting were made, is an isolated 
island with a very clannish community that has never really accepted any 
residents from Europe, British administrative people or missionaries on the 
island. We have good evidence that our own sojourn was the first that had 
been spent overnight. 

Chaieman Dr. Cronheim: One question that I only want to mention 
because there is apparently some misunderstanding, says : "Wliat is known 
of the chemistry or pharmacology of Kava Kava as distinct from Kava?" 
They are two terms for the same plant and the same material. 

The next question is directed to Drs. Meyer, Pf eiffer and Buckley : "Dr. 
Pfeiffer dound dl-dihydromethysticin effective for only major sezures. Dr. 
Meyer, on the other hand, found it to behave like the diazopans, which are 
more effective in all but major seizures ?" 

Dr. Meyer: I think there must be a mistake here, since I never quoted 
on the anticonvulsive effectiveness of the benzodiazepines which is indeed not 
very strong, at any rate much weaker than is found with the Kava pyrones. 
What I compared, however, was the muscular relaxant activity of both groups 
of drugs which is produced likewise by a central, most likely supraspinal 
mechanism of action. 

Dr. Buckley : None of our work has been done on this problem, and the 
only finding we have to corroborate the work of Dr. Meyer is that the water 
soluble material that we are working with is a very potent muscle relaxant. 

Dr. Pfeiffer : If one compares in animals the effect of chlordiazepoxide 
against the Kava principles, the Kava has an anti-strychnine effect, and the 
chlordiazepoxide is barbiturate-like and has an anti-Metrazol effect. One 
can use both of them in epileptic seizures since the patients who are not re- 
sponding to classical anti-epilepsy therapy have usually mixed epilepsy, and 
one can get a variety of beneficial effects. Our sample was at the most twelve 
patients. In these the predominant effect was a decrease of grand mal seizures 
and no change in their minor seizures. Had we had a larger sample, and had 
we done a careful comparison with chlordiazepoxide, we might have found 
different results. 

Chairman Dr. Cronheim : Here is another question : "Why is the char- 
acteristic Easter Island wooden statue of a man called Moa Kava Kava?" 
Maybe Dr. Holmstedt who sent in this question can provide also tlie answer. 

Dr. Holmstedt: No. 

Chairman Dr. Cronheim : The next question, which perhaps can be an- 
swered by our anthropologist friends, who have seen the effects of Kava, 
is as follows: "Are cola drinks adequate substitutes for Kava insofar as 
claimed effects are concerned ? " 

Dr. Ford : I suppose that by cola drink you mean soft drinks such as Coca 
Cola or Pepsi Cola. All I can say is that in my experience with the Fiji 
people, men particularly, would rather drink Kava than either a soft drink, 
such as the colas, or beer. That does not mean to say that they won't drink 
cola, but I am quite certain that there is a distinct preference for Kava, and 



176 



had if they had to choose one as opposed to the other, they would take their 
own native drink. 

Chairman Dr. Cronheim : The next question is to anyone on the panel : 
"Is there any specific therapeutic use of Kava by natives, or does any occur 
to you?" This can be answered by anyone on the panel. (No answer was 
forthcoming.) 

Dr. Pfeiffer : I have a question, and that is, since griseof ulvin is fungi- 
cidal and deposits in the skin, I think it would be of interest to determine 
if there is any fungicidal effect of any of these Kava principles, because 
we know in this particular area of the world "jungle rot" or fungal infections 
are very common, so that the incidence of fungal infections might be less 
in the male than in the female. 

I have already brought up the question of whether or not it is a pain killing 
drug and the consensus seems to be that it is not a pain killing drug in general. 

Dr. Holmes : I did mention this morning that it is often taken to relieve 
the chills of filariasis, but other than that I know of no claims for Kava as 
a therapeutic drug. 

Dr. Buckley : I can mention that the preliminary data that we have on 
the aqueous subfraction F-1 of Kava, indicated by the pharmacologic pro- 
files, would suggest that if we are ever able to isolate the active constituent 
that it has potential tranquilizing activity, if it is effective orally. 

Chairman Dr. Cronheim: The next question is directed to Dr. Meyer 
and Dr. Buckley : "Since Kava ingestion causes a soporific effect, coupled 
with loss of muscle tone, have any studies been carried out relating the 
active principles of Kava to the physiological mechanisms of sleep in general, 
and to REM-sleep in particular ?" 

Dr. Buckley: I will introduce the subject. Data that we have obtained 
indicate that in the dosages used we get a very marked sedative effect, but not 
an effect as far as inducing sleep. These animals are very alert, and it appears 
that the reaction is at the subcortical level rather than the cortex. It is only 
when we get up to the higher doses that we get a true effect on the spinal cord 
and on the cerebral cortex. 

Dr. Meyer : One of the most striking manifestations during sleep revealed 
by electrophysiological recording is the reduction in the activity of skeletal 
muscles. In our experiments with Kava constituents of the pyrone group, 
we found a decrease of the tonic properties of the alpha motoneurones, 
followed by a loss of muscle tone which may resemble in some respect the 
reduced muscular activity observed in sleep. 

On the other hand, there is no effect, no depressing effect, on the arousal 
response of the cerebral cortex elicited by electrical stimulation of the mid- 
brain reticular formation, which is in contrast to the depressant action of the 
barbiturates on this system. We think that this is an appreciable difference 
between hypnotics and soporific agents like the Kava pyrones, the action of 
which are apparently more related to the physiological mechanisms of sleep. 
Moreover, animals put into sleep by Kava pyrones, easily can be aroused at 
any time of drug action. 



177 



Investigations with pyrones related to KEM-sleep have not been carried 
out so far. 

Chairman Dk. Ceonheim : I have a question here to Dr. Ford and the 
rest of the panel: "Would you please expand on the comment you made 
concerning possible enhancement of mental ability. Do any of the members 
have anything to add on this subject ?" 

Dr. Ford : Well, all I can say is what I said before, and this is, of course, 
very tenuous judgment; but it did seem to me that the Fijians were just as 
alert, if not more alert, while they were drinking Kava, than when they were 
not. 

It may be that other aspects of the situation account for part of this. For 
example, decision-making and considering future plans of the villagers might 
help to provide this alertness rather than the Kava itself. 

From my own experience, and here again I think there might be individual 
differences, I never felt that Kava affected my thinking. Our youngest son, 
who was twenty-three years old at the time, came and spent two months with 
us in Naviti. The young men of the village sort of challenged him to Kava 
drinking bouts, much as beer drinking bouts might take place among such 
young people here. He claims that during the first half hour of such a drinking 
bout, during which he consumed maybe a quart or so of this diluted Kava, 
he became quite drowsy and sleepy, but that after this period passed he was 
well alert and wide awake enough to actually speak Fijian better than he 
felt he had normally been able to do. 

Dr. Gajdusek: I just never felt this drowsy feeling, and I don't know 
what the answers to this might be. The Tongarikans obviously are not 
drinking Kava socially. Often they are drinking alone. They are anxious to 
get the expected effect, and therefore having taken a large dose and eaten, 
and if they are not getting the effect, they often go back and have their boys 
chew more. They are subjectively evaluating what is happening; and if a 
sufficient reaction is not observed within the first half hour, they drink more ; 
they raise the dose. 

Those who are obviously casual drinkers, like myself, are likely to get a 
half portion, they are a little stingy about the Kava, they don't want to waste 
it on those who don't enjoy it, and with that half dose I could leave the area, 
go back to whatever work I was going to do that evening without any notice- 
able subjective impairment; and my colleagues do the same. 

Wlien one pushes the point and tries several doses one does get an effect. 
It is the effect I described : there is a market paresthesia of the lower ex- 
tremities, numbness and cooling. It is not real anesthesia ; you can still feel 
sensations with the extremities. 

The men describe the same effect and they don't want to be disturbed as 
they subjectively observe it. They like the feeling and they refer particularly 
to numbness of their lower extremity up to the waist. They claim, and we 
find this to certainly be the case, that when one takes enough and tries to 
get up, one falls on one's face. They still have reflexes at this stage as I looked 
at them, but there are plenty of men who leave for home at too early a stage. 



178 



and need assistance to go home. They fall off the trail, but these are people 
who are concerned about their Kava and are drinking plenty of it. 

Two other items which I think pharmacologically ought to be kept in 
mind. There is a great deal of concern whose Kava one is using, what garden 
plot it comes from, whether it is too dry, or if it is grown in the wrong soil 
or in the wrong place. I wonder whether one may not have a variety, depend- 
ing on growth and hvdration of the roots. 

Chairman Dr. Cronheim: I have a short question to Dr. Pfeiffer, and 
then one to the panel. The question to Dr. Pfeiffer is: "How would one 
reconcile the arousal or excessive cerebral activity of schizophrenics with 
the apparent decrease of synaptic transmission shown in the cat?" 

Dr. Pfeiffer: This represents two different test preparations, one the 
pentobarbitalized cat as a model on which to test hallucinogenic drugs. The 
other represents the natural state of psychosis in unanaesthetized patients. 
There is such a world of difference that I don't think one can compare the 
two, except in an average overall sample of brain wave activity. The brain 
wave of the schizophrenics are those of an over aroused or hyper- regulated 
type. 

In regard to the previous question on performance under Kava, which 
asked if the mind was more clear, we know of many colleagues who are 
constantly over-stimulated and do their best when they have a sedative 
in them, whether it be meprobamate, chlordiazepoxide, or bourbon. I know 
one very fine author who can only write a book consuming a case of bourbon 
a week. It is a very fine book and this is the way the man works; he is 
productive on whiskey but not otherwise productive. 

Chairman Dr. Cronheim: I have two more questions, both pertaining 
to the same subject, and I am going to read them and will add to these 
questions one additional point, and then we will have to stop this discussion 
because of the time factor. 

One question reads : "Will one of the speakers trace the introduction and 
migration of the beverage throughout the Pacific? Is it used throughout 
the range of the plant? What cultural modification of the natural range 
took place in the Pacific ?" 

The other question reads : "Dr. Ford mentioned parallel distribution and 
use of Betel and Kava, but cited as an example that in Tikopia, Betel was 
chewed, whereas Kava was poured on the ground. Parallel distribution of 
plants occurs in Micronesia, but usage is not parallel. Would Dr. Holmes 
care to comment on this?" I think in line with this, perhaps the most 
important, the most interesting question is a kind of summing-up question, 
namely : 

We have heard from Dr. Gajdusek some very definite experiences of Kava 
effects that he has observed both on himself, on his associates, and also on 
the natives in the Islands where he worked. We have heard from Dr. Ford 
and Dr. Holmes that they did not see such effects or did not experience 
them on themselves ; and so to relate it to the questions I just read to you, 
can the three of you in some way point out the differences, either in the 
time of the year or the type of the plant ? Is it really botanically the same 



179 



plant, or are there other differences, conceivably other than the question 
of dosage that Dr. Ford already mentioned? Could you explain this very 
apparent dichotomy ? 

Dk. Holmes: I would like to answer that last question, because I would 
hate to try and trace the distribution in the short time we have. We did 
attempt to do a bit of this in our papers. But there are a couple of things 
I would like to say about this last question: I think we ought to resolve 
these problems, or at least attempt to do so. I would think that part of 
the answer might rest in the amounts, or concentration. The Kava ceremony 
that you observed in my film involved about as much Kava as would fill 
my hand level. I have no measurements of this. It is a very rough estimate. 
This would be placed in a fairly large bowl about sixteen inches across. 
I imagine there would be close to a gallon of water in there, because some- 
times as many as thirty Chiefs will be served a cup of Kava, and the cup 
is pretty good sized. It might be that it is much more diluted in some places 
than in others. 

There is the possibility of the saliva factor, and I might comment on this. 
The Kava that I have seen drunk and have drunk myself was not chewed 
and therefore did not involve saliva. I did not mention this in my talk this 
morning, but formerly Kava was prepared by chewing in Samoa also. How- 
ever, all of my informants told me that the Kava chewers were trained not 
to get saliva on the Kava. I don't know how you do this, but the attempt 
was made not to get a big, messy cud and to keep the Kava as dry as possible. 
Apparently, at least according to my informants, the attempt was made not 
to get too much saliva in the mixture. 

Dr. Ford: A relatively amusing thing happened back ui the early 
1860's. The missionaries got disturbed about the fact that in parts of Fiji, 
particularly along the coast, they chewed the Kava root in preparation, and 
one fellow thought he had clinched things. What he did was to weigh pieces 
of Kava root before they were chewed and then swipe them from the 
chewer before he packed them back into the bowl; and from six ounces 
of Kava root, it increased to seventeen ounces after having been chewed. 
This was used as a stock example by everybody to justify stamping out this 
horrible, detestable habit of pre-masticating Kava. I have never tasted Kava 
that has been pre-masticated and this would seem to be one variable. 

Another is the variable of the green versus the dry root. 

Another is the variable of maybe different varieties in different soils, and 
the final one is obviously the tremendous difference in the amount of 
concentrate. 

Dr. Gajdusek: The dosage matter is very important. The quantity of 
Kava you are describing is less than is used in Tongariki for one man, let 
alone for thirty Chiefs. A large quantity sufficient for six young men is 
made, and I suspect this amount of root is more than you are using for 
your whole ceremony. This is one person's production. 

From the Floor: Did the chewers get a KaA^a effect? 

Dr. Gajdttsek : The yomig men that are chewing the Kava have a thor- 
oughly anaesthetized mouth. They claim that they cannot taste anything for 



180 



the rest of the evening. They also have a stiff mouth and claim they have 
difficulty in articulating. 

Dr. Leake : We should always remember that the active principles in any 
plant vary enormously with respect to the soils in which they may grow. 
This is well known with nicotine and tobacco, or ephedrine. This may be a 
factor in the variation in Kava, since the soils in those areas do vary greatly. 

Dr. Holder (from the floor) : I am an anthropologist from the Univer- 
sity of Nebraska. In 1943 on the Northern New Hebrides Islands, I drank 
Kava and helped prepare it, and in Dr. Gajdusek's comments and other 
comments this might be worthwhile. The Kava was dried and smoked in 
the roof timbers, and the preparation Avas made by taking a piece about 
twice as large as your thumb and chewing it for about three to four minutes. 
The natives themselves said it was necessary to get the saliva in to release 
the active principle. 

I had been chosen as a chewer and did chew on many occasions, and I got 
anaesthetized tongue and the inner lining of my mouth was anaesthetized. 
This chewed mass was mixed with water in cocoanut cups and from four to 
five people drank; and it was chewed again. There was a marked diuretic 
effect; everybody had to leave about every twenty minutes, as in drinking 
beer. This was social, but the total effect was to loosen tongues and to talk 
far into the night, and no hangover the next day. There was absolutely none 
of this depression, and here again, these were small doses. 

This was on the Island of Espiritu Santo on the southern slope of Mount 
Santo, at a village called Batuito at about five thousand feet, and they told 
me that in the past Kava had been used as part of the sexual ceremony, 
which was jDOured over a stone phallus prior to being mixed and drunk. 

Dr. Gajdtjsek : Jean Guiart, our colleague who worked both in Santo 
and Malakoa, never himself experienced any reaction from the Kavas on 
Malakoa. 

Chairman Dr. CronhEiIm:: We have already exceeded by ten minutes 
the time allotted to us, so it is witli great regret that I have to close the 
discussion. 

I want to thank all the participants for a most enlightening and most 
stimulating panel. 



181 



SESSION in 



MYRISTICA FRAGRANS (NUTMEG) 

Edward B. Truitt, Jr., Chairman 



Chairman's Introduction 



Edward B. Truitt, Jr. 

Battelle Memorial Institute, Columbus, Ohio 

In this introduction, I would like to formulate several questions which I 
believe are crucial for this section of the program. The presentations to fol- 
low will likely answer very few of these questions. Rather, I think, the juxta- 
position of these questions with the scanty information so far collected about 
the physical and physiological actions of nutmeg will emphasize the real 
need for further research into the dietary, ritualistic, and drug-seeking habits 
of man with this spice, and their possible significance. 

The uppermost question that plagues the conscious of an investigator in 
this field is whether, by discussing publicly a substance with a potential for 
abuse by the lay public, he is inadvertently opening another Pandora's box 
of human ills. One answer to this question, in the case of nutmeg, appears 
to be that this substance has enough unpleasant effects mixed with its cen- 
trally stimulating actions to discourage misuse by any but the most reckless 
psychodelic adventurers. This will certainly be borne out by the reports to 
follow about the toxic effects of human overdose by ground nutmeg in the 
crude drug form. Whether the same will be true of myristicin or other active 
components of the volatile fraction will need to be learned, because experi- 
ence with the purified products is quite meager. A lesson from LSD should 
be applied here, so that the human risks of nutmeg derivatives, mental as 
well as organic, will be carefully evaluated by clinical pharmacologists in 
anticipation of the possibility of widespread misuse. 

A second question might appraise the need for further investigation on 
a substance which appears to be another stimulant to a central adrenergic 
receptor already affected by mescaline, cocaine, the amphetamines, epine- 
phrine, adrenochrome, and possibly by LSD and other tryptamine-like 
hallucinogens. An answer to this question certainly lies in the importance 
of the study of structure and activity variations. Pharmacologists and medi- 
cinal chemists are strong advocates of the advisibility of characterizing drug 
activity in terms of the effects of structural changes in the molecule. Thus, 
we should look in the session to follow for those clues to variation in the 
central activity produced by myristicin, which has a slightly different for- 
mula from mescaline, as shown in Figure 1. 

Myristicin is unique among psychotropic agents in that it lacks a nitrogen 
atom. This unusual characteristic has led Dr. Shulgin to propose an inter- 
esting hypothetical mechanism for its action which I am sure he will find 
time to discuss. 

Another question which can be asked is how the information to be presented 
here on nutmeg and myristicin can be helpful to a better understanding of the 
workings of the mind. Since a partial answer to the previous question ap- 
pears to be that nutmeg intoxication is in some ways different from mescaline 



262-016 0-67— 14 



185 



Mjrristicin (5-allyl-2,3 methylenedioxyphenylmethyl ether or 
3-methoxy-4,5-methylenedioxyallylbenzene) 

CH3O 
I 



0— < ^ ^ ^CH;CH=CHi 

I I 
CH2-O 

Mescaline (3,4,5-trimethoxyphenylethylaniine) 

CH3O 
I 



CH3O— < >— CHjCHi— NH2 



I 

CH3O 

FiGUKE 1. — Structural formulas of myristicin and mescaline. 



and similar drugs, how does this difference contribute to better understand- 
ing ? What is the relationship between the central feelings of anxiety, detach- 
ment, and excitation with somatic effects such as tachycardia, xerostomia, 
hypothermia, vasomotor lability, pupillary changes, and heaviness of the 
limbs ? The marked degree and variety of peripheral effects prompts the ques- 
tion as to how much of the psychic action is attributable to the centripetal 
stimuli. 

From a therapeutic viewpoint, one might ask whether some aspect of the 
syndrome induced by nutmeg might have a therapeutic application. This is, 
indeed, the most central question to the purposes of this conference. How- 
ever, this goal has not yet been achieved for any of the drugs presently 
labeled as hallucinogens. Another useful advantage of this discussion could 
be the recognition of a means of treating nutmeg intoxication which occurs, 
although infrequently, and may be expected to increase. 

The program to follow cannot begin to treat all aspects of nutmeg 
because extensive communication with other scientists and reviews of the 
scattered literature did not lead to the finding of experts on the anthropogical 
and other facets of the spice. It is perhaps appropriate that a pharmacologist, 
such as myself, inherited the chairmanship of this section. The reason for 
this is that three of the major early investigators, Arthur Cushny, Sir Henry 
Dale and George Wallace were all pharmacologists, and venerable ones also. 

The first speaker, Mr. Andrew T. Weil, has produced perhaps the most 
detailed review of the nutmeg literature while essaying his honors thesis 
in botany. (1) Following this introductory review. Dr. Alexander T. Shulgin 
will describe research which already has put into practice one of the objec- 
tives of this conference. Dr. Shulgin and his associates have used the em- 
pirical observations of psychopharmacological activity in nutmeg and 
mescaline as a starting basis for the synthesis and testing of newer, more 
active and varied psycho-active drugs. Dr. Shulgin has also surpassed every- 
one for continued interest and publications on myristicin {2-9). My OAvn 
interest in the action of nutmeg emerged from Dr. John C. Krantz's scientific 
curiosity in response to several cases of nutmeg poisoning referred to him 
by graduates of the University of Maryland Medical School. {10) It was 



186 



also continued by the then-growing importance of norepinephrine and 5- 
hydroxytamine in brain function. {11) The last speaker, Dr. Enoch Calla- 
way, III, is an authority on nutmeg by reason of personal experience as well 
as having conducted clinical experimentation with a purified myristicin- 
containing fraction of oil of nutmeg. {10) I believe that his experience 
with the drug, if widely known, should certainly dissuade public abuse of 
nutmeg. 

BIBLIOGRAPHY 

(1) Weil, A. T. "Nutmeg as a Narcotic." Economic Botany, 19 : 194, 1965. 

(2) Shulgin, a. T., S. Bunnell, and T. Sargent, III. "The Psychotomimetic Prop- 

erties of 3, 4, 5-Trimethoxyamphetamines." Nature (Lond.), 189: 1011, 1961. 

(3) Shulgin, A. T. "Composition of the Myristicin Fraction from Oil of Nutmeg." 

Nature (Lond.), 197 : 379, 1963. 
(Jf) Shulgin, A. T. "Psychotomimetic Agents Related to Mescaline." Experientia, 19: 
127, 1963. 

(5) Shulgin, A. T. "Concerning the Pharmacology of Nutmeg." Mind, 1: 299, 1963. 

(6) Shulgin, A. T., and H. O. Kerlinger. "Isolation of Methoxyeugenol and Trans- 

I'soelemicin from Oil of Nutmeg." Naturwissenschaften, 15 : 360, 1964. 

(7) Shulgin, A. T. "3-Methoxy-4,5-Methylenedioxyamphetamine, A New Psychotomi- 

metic Agent." Nature, 201 : 1120, 1964. 

(8) Shulgin, A. T. "Psychotomimetic Amphetamines: Methoxy-3,4-Dialkoxy Amphet- 

amines." Experientia, 20 : 366, 1964. 

(9) Shulgin, A. T. "Possible Implication of Myristicin as a Psychotropic Substance." 

Nature (Lond. ) , 210 : 380, 1966. 
(JO) Truitt, E. B., Jr.. E. Callaway, III, M. C. Braude, and J. C. Krantz, Jr. "The 

Pharmacology of Myristicin. A Contribution to the Psychopharmacology of 

Nutmeg." Journal of Neuropsychiatry, 2 : 205, 1961. 
(11) Truitt, E. B., Jr., G. Duritz, and E. M. Ebersberger. "Evidence of Monoamine 

Oxidase Inhibition by Myristicin and Nutmeg." Proceedings of the Society for 

Experimental Biology and Medicine, 112 : 647, 1963. 



187 



Nutmeg as a Psychoactive Drug 



Andrew T. Weil 

Harvard Medical School, Boston, Massachusetts 

Clearly, nutmeg is unique among the less familiar psychoactive drugs. It 
is the only one widely known to millions of persons in all countries — albeit 
for other-than-pharmacological purposes. It is also the only one whose use 
as a drug may be on the verge of an enormous increase. The aim of this paper 
is to review the botany, history, and commerce of nutmeg as well as to describe 
the ways it is used for effects on consciousness. 

Two spices — nutmeg and mace — come from the nutmeg tree, Myristica 
fragrans (family Myristicaceae) , a handsome tropical tree native to the 
Banda Islands and other islands of the East Indian archipelago. The genus 
Myristica comprises about 100 species found throughout the torrid zone, 
especially in the Malayan region; but of these M. fragrans alone contains 
enough of an aromatic essential oil to make it worthy of cultivation. Usually 
30 or 40 feet tall, the nutmeg tree has a dark gray bark, spreading branches, 
and alternate, oblong-ovate leaves that are four inches long, leathery, and 
glossy green. Normally, the species is dioecious. Flowers, male and female, 
look like those of the lily-of-the- valley ; they are pale yellow, fleshy, and have 
a strong scent of nutmeg. The fruit is a pendulous, fleshy drupe resembling an 
apricot {1,2,3). 

When ripe, the fleshy husk, or pericarp, of this fruit splits open into two 
halves, revealing a shiny brown seedcoat, or testa. Inside this shell is the seed, 
which is the nutmeg of commerce. Outside the shell, closely enwrapping it, 
is a bright crimson network, or arillus, which is the mace. In preparing the 
spices for export, fieldworkers first remove the pit with its mace from the 
husk. The aril is then carefully peeled away from the seedcoat. Fresh arils 
are brilliant red and leathery with a strong flavor of turpentine. The mace 
may be kept in one piece (called "double blade" in the trade) or separated 
into two halves ("single blade") before it is flattened by hand or between 
boards. It is then dried thorouglily in the sun or by artificial heat; during 
this process it gradually turns orange, then orange-yellow and acquires its 
characteristic aroma (3, 4-) • 

The nutmegs, still in their shells, are also dried, frequently over a smoulder- 
ing fire. "Wlien completely dry, the seed rattles in the testa. Usually the shells 
are then cracked by machine or with wooden mallets and the seeds are re- 
moved for export. Sometimes, shelled nutmegs are treated with lime before 
shipping to protect them from insects. They are then sorted by size and 
packed. For the spice trade, nutmegs are valued according to size, smoothness, 
and freedom from adulteration with wild seeds {2,4-)- 

The nutmeg tree requires a hot, humid climate. It is widely cultivated in the 
tropics, particularly on the Spice Islands (the Moluccas, an island group of 
eastern Indonesia), on Penang and other islands of Malaysia, and in the 



188 



Caribbean, notably on Grenada. The tree is slow-growing, taking 15 years to 
produce full yields. A good specimen produces 1,500-2,000 nuts annually — a 
weight of ten pounds of nutmeg to one-half pound of mace. The finest mace 
and the finest nutmegs come from Penang; because of their higher content of 
volatile oil, the East Indian spices are preferred to the West Indian (4.) . 

Products of M. Fragrans 

Nutmeg HusJcs: The pericarp of the nutmeg fruit may be preserved in 
sugar, salted and dried as a condiment, or made into jellies. All of these prepa- 
rations have the flavor of nutmeg and all are reported to be delicious. But they 
are unknown outside the regions in which the tree is grown {2,3). 

Nutmeg: Whole nutmegs are oval and woody with a ridged or wrinkled, 
light brown surface. Most are about an inch long, three-quarters of an inch 
in diameter. On cross section they show a heavy network of dark brown 
"veins." Ground nutmeg, the familiar kitchen spice is a granular, orange- 
brown powder with characteristic aroma. 

Depending on the variety, whole nutmeg contains from 5 to 15 per cent of 
a volatile oil that accounts entirely for the aroma and flavor of the spice. 
Ground nutmeg is subject to rather rapid losses of this component. In addi- 
tion, dried nutmeg contains 25 to 40 per cent of fixed oil and 5 to 15 per cent 
ashes. The remainder is moisture, fiber, and starch {5). In the calendar year 
1965, the United States imported nearly 5,300,000 pounds of nutmeg worth 
about $3,800,000. Of this total, nearly 72 per cent came from Indonesia, while 
24 per cent came from the Caribbean, with the remainder from a number of 
smaller ports. Imports over the past ten years have been fairly constant 
(Table I), but there has been a change in the major source of this spice. 
Until 1955, the U.S. obtained about half of its annual supply of both nutmeg 
and mace from the West Indies. In that year, however, a hurricane devastated 
the island of Grenada, and the nutmeg groves there have still not recovered 
from the damage {6). 

Mace: Mace, another popular spice, is a brownish-yellow or brownish- 
orange granular powder with a strong aroma closely resembling that of nut- 
meg. The flavor of mace is somewhat less sweet and less delicate than the 
flavor of nutmeg. Whole mace contains from 4 to 14 percent of a volatile oil 
very similar to that found in nutmeg, along with moisture, fat, starch, etc. 



Table I. — U.S. imports of nutmeg and mace* 
[pounds] 





Average 


Average 


Average 


1963 


1964 


1965 




1950-54 


1955-59 


1960-64 








Nutmeg 


4, 852, 221 


4, 141, 074 


4, 151, 480 


5, 124, 638 


3, 505, 450 


5, 271, 524 


Mace 


658, 193 


549, 072 


563, 874 


558, 541 


648, 900 


619, 394 



*Source: U.S. Department of Commerce, Bureau of the Census Compilation by American Spice Trade Association. 



189 



{5; 7, Vol V) . In 1965, the United States imported 619,000 pounds of mace 
worth S750.000. Seventy-six percent came from Indonesia, the rest from 
Malaysia, Hong Kong, Japan, and the Caribbean. As with nutmeg, imports 
of mace have not varied much over the past ten years (Table I) . 

Uses of Nutmeg and Mace: Both spices are classified as "baking spices" 
since they are much used in foods like doughnuts and other sweet doughs. 
Both have a warm, aromatic, slightly bitter taste. Xutmeg is commonly 
added to custards, puddings, pies, and eggnog. Mace is used in soups, sauces, 
and pastries, particularly pound cake. In addition, both spices are important 
ingredients of frankfurters and other meat products, pickles, tomato ketchup, 
and similar condiments. The American Spice Trade Association estimates 
that 55 percent of nutmeg and mace imported into this country is sold 
through retail stores to home consumers. The rest goes to institutions (hotels, 
restaurants, bakeries, sausage manufacturers, and other bulk users). For- 
merly, housewives bought whole nutmegs and grated them at home : today, 
most of the nutmeg and all of the mace sold for home consumption is ground. 

Fixed Oil of Xutmeg : Known also as "nutmeg butter," this vegetable fat 
is obtained by exposing the nuts to hydraulic pressure and heat. At room 
temperature, it is an orange, tallowy mass with a pronounced aroma of 
nutmeg and the consistency of butter. Formerly used in medicine as an ex- 
ternal application for rheumatism and sprains, it has some commercial im- 
portance today as an ingredient of certain soaps, hair tonics, and perfiunes 
{2,3,5). 

Essentiol Oils of Nutmeg and Ma^e: The essential or volatile oils of nut- 
meg and mace are obtained by steam distillation. Commercial oil of nutmeg 
is a mobile, pale yelloAv liquid with an odor and flavor of nutmeg. It is not 
satisfactory as a substitute for the spice in cooking because it does not 
exactly reproduce the flavor of whole nutmeg. ("Essences" of ntttmeg and 
mace sold by spice dealers are alcohol extracts not essential oils.) But oil of 
nutmeg has been widely used in industry as a flavoring agent for perfumes 
and dentifrices. Chemically, it is a complex mixture of alcohols, esters, and 
organic acids, including about four percent myristicin, the main pharmaco- 
logically active component (7. Vol V : <S : 5) . 

History of Nutmeg 

Xutmeg was unknown to the ancient Greeks aiad Romans, but probably, 
Arabian tradei-s began importing it from the East Indies by the first centuries 
A.D. No definite evidence of Myristica's appearance in Europe is recorded 
imtil the 12th Century, and the source of nutmeg was not discovered by the 
West until the Portuguese reached Banda in 1512. Portugal controlled trade 
in nutmeof and mace from that vear until the beginning of the 17th Century, 
when most of the Pacific spice-producing territories fell into the hands of 
the Dutch. In order to keep prices of the spices very high, the Dutch tried 
to limit cultivation of the nutmeg tree to two islands, but their monopoly 



190 



was eventually challenged successfully by the French and British. Gradually, 
commercial development of M. fragrans spread throughout the world, reach- 
ing Grenada, for example, in 1843 {3) . 

Like most aromatics, nutmeg was as important in early medicine as it was 
in cooking {10) . Its therapeutic applications were first catalogued by Arab 
physicians as early as the 7th Century A.D. Originally, it seems to have been 
a remedy for disorders of the digestive system, but before long it was con- 
sidered beneficial in such diverse conditions as kidney disease, pain, and 
lymphatic ailments ; it was even described as an aphrodisiac. Many of these 
beliefs are preserved in contemporary Arab folk medicine ; in fact, Yemenite 
men still consume it to increase virility. 

Similarly, nutmeg was and is a significant item in the Hindu pharma- 
copeia, where it has been prescribed for fever, consumption, asthma, and 
heart disease. Traditional Malayan medicine designates nutmeg for madness 
as well. According to an adviser in the Indian Ministry of Health, nutmeg 
is still used as an analgesic and sedative by folk practitioners, and is given 
in small quantities to induce hypnotic effect in irritable children. 

Medieval European physicians, who generally followed the precepts of 
their Arab colleagues, also prescribed nutmeg for a long list of ailments. By 
the l700's the spice attained its greatest reputation ; thereafter, with the de- 
velopment of modern pharmacy, its importance as a medicine gradually 
subsided. 

Curiously, nutmeg's popularity as a folk remedy had a brief, spectacular 
resurgence less than one hundred years ago. Near the end of the 1800's, a 
rumor spread among women in England and America that nutmeg could 
bring on overdue menstruation and even induce abortion. The origin of this 
mistaken belief is unclear, but its influence is well documented in dozens of 
case reports of nutmeg poisoning published in British and American medi- 
cal journals of the period {10). The idea has even persisted into our times: 
Green in 1959 wrote of a 28-year-old Virginia woman who ate "18.3 Gm. of 
finely ground nutmeg in an attempt to induce the menses, which had been 
delayed two days ." 

Reports of nutmeg poisoning date back to the late Middle Ages when 
several early physicians first wrote down their observations on the stupor- 
inducing powers of the spice. Doubtless, most of these intoxications resulted 
from overdoses taken as remedies. A late example comes from A Treatise 
on the Materia Medica written in 1789 by an English physician, William 
CuUen. He wrote : 

I have myself had an accidental occasion of observing its [nutmeg's] soporific and 
stupefying power. A person by mistake took two drams or a little more of powdered 
nutmeg ; he felt it warm in his stomach, without any uneasiness ; but in about an hour 
after he had taken it, he was seized with a drowsiness, which gi'adually increased to 
a complete stupor and insensibility ; and not long after, he was found fallen from his 
chair, lying on the floor of his chamber in the state mentioned. Being laid abed he fell 
asleep ; but waking a little from time to time, he was quite delirious : and he thus con- 
tinued alternately sleeping and delirious for several hours. By degrees, however, both 
these symptoms diminished, so that in about six hours from the time of taking the 



191 



nutmeg he was pretty well recovered from both. Although he still complained of head- 
ache and some drowsiness, he slept naturally and quietly through the following night, 
and next day was quite in his ordinary health. 

There is no doubt that this was entirely the effect of the nutmeg. . . . 

In 1829, the great physiologist J. E. Purkinje conducted self -experiments 
with nutmeg. Following a dose of three whole nutmegs, he experienced 
spatial and temporal disorientation similar to that of Camaabis intoxication. 
He wrote {12): 

At half-past six. when it was almost dark, I woke up in order to go to the Royal 
Theatre at Brueder Street where I lived. The distance was long, but this time I thought 
it had no end. My movements api)eared entirely adequate, but were lost momentarily in 
dream pictures, from which I had to extricate myself with considerable force in order 
to keep on walking. My feet did their duty and, since I had to stick to a straight road, 
there was no danger of going astray. I went forward in this dream, for, if I attempted 
to orient myself, I could not even recognize the cross streets. Time seemed long, but I 
got to the opposite side of the place where I was going. During this time dreams and 
physical activity battled one another. The return journey was good, and I slept well 
that night and next day. 

There is a similar, more dramatic report of mace intoxication from 1848 
{13) . But as stated earlier, the greatest numbers of peo^^le poisoned by 
Myristica have been English and American women of the late 19th and 
early 20th Centuries. Summarizing many of these cases in 1962, McCord 
wrote (14-) '■ 

. . . patients have consumed from 1 to 3 nutmegs and have experienced restlessness, 
dizziness, fear of death, coldness of extremities, occasional nausea and vomiting, 
abdominal pain, and precordial pain or oppression. These patients were found to be 
extremely agitated, delirious, and dyspneic and have had weak, rapid pulses and de- 
creased body temperature. On several occasions patients were found unconscious. Oc- 
casionally there was flushing of the face while at other times pallor with cyanosis of 
the lips and nails predominated. 

He attributed these intoxications to "a central nervous system depressive 
effect with periods of stimulation and associated respiratory and cardio- 
vascular difficulties."" 

Only one fatality has ever been ascribed to nutmeg ingestion: near the 
begimiing of this century, an eight year old boy ate two whole nutmegs, 
became comatose, and died less than 24 hours later (IS) . 

Use of Nutmeg as an Intoxicant 

The apparent epidemic of nutmeg intoxications aroiuid the turn of the cen- 
tury subsided after the First "World "War. Cases since then have been rare. 
In 1963, Payne presented one of the only published reports of deliberate 
ingestion of Myristica for narcotic effects. He described two college students, 
19 and 20 years old. Avho each consumed two tablespoonfuls (about 14 g. 
or the equivalent of two whole seeds) of powdered nutmeg suspended in 
milk {16). About five hotirs later 

. . . each had the onset of a significant pharmacologic effect, heralded by a leaden 
feeling in the extremities and a nonchalant, detached mental state described as 'un- 
real' or 'dreamlike.' Rapid heart rates and palpitation were noted, and both complained 



192 



of dry mouth and thirst. Onlookers observed that one student became quite hyperactive 
and agitated and talked incoherently. It was noted that the faces of both vyere as 'red as 
beets.' Nausea, vomiting, and abdominal cramps were absent. . . . One described a sense 
of impending doom, as if he were 'breaking up inside.' 

Extreme drowsiness occurred about seven hours after these symptoms 
began and continued for the next 24 hours. Recovery was complete, but "both 
patients stated emphatically that a sense of unreality persisted for 48 to 60 
hours from the time of one oral dose of nutmeg." 

A history of the use of nutmeg for the express purpose of inducing these 
bizarre physical and mental effects is hard to piece together simply because 
reliable data on Myristica narcosis are not available. The medical literature 
is of no help, for example, because nearly all the reported cases have resulted 
from accidental ingestions or overdoses taken as remedies. Most of the in- 
formation on nutmeg as a psychoactive drug is anecdotal, and it has been 
most difficult to document the anecdotes. 

Stories in circulation about nutmeg at the present time develop several 
recurrent themes. One is that Myristica is used as an intoxicant in certain 
parts of Asia. Another is that nutmeg is widely consumed by prison inmates 
in this country. A third is that students and 'beatniks' have adopted the 
the spice as a new hallucinogen. 

For the first story little supporting evidence can be found. A suggestive 
clue is one of the synonyms for nutmeg used in Ayurveda, an ancient Hindu 
scripture. Here, nutmeg is called Mada shaunda meaning "narcotic fruit." 
There is reason to believe that nutmeg is, in fact, eaten as an intoxicant even 
today by some people in India who add it to betel chew. It may also be mixed 
with tobacco and snuffed in this part of the world. Equally vague is a report 
that nutmeg is taken as a stimulating snuff by natives in remote regions 
of Indonesia. Still another unsubstantiated assertion is that nutmeg is often 
substituted for hashish in Egypt when the hemp product is not available. 

It is much easier to confirm rumors of nutmeg use by prison inmates, 
despite denials by prison officials. One interesting reference occurs in 
The AutoMography of Malcolm X (17), in which the late Black Muslim 
leader describes his incarceration in a Boston prison in 1946. He was then 
a user of marihuana and other drugs and found himself suddenly cut off 
from them. He wrote : 

I first got high in Charlestown [prison] on nutmeg. My cellmate was among at 
least a hundred nutmeg men who, for money or cigarettes, bought from kitchen- 
worker inmates penny matchboxes full of stolen nutmeg. I grabbed a box as though 
it were a pound of heavy drugs. Stirred into a glass of cold water, a penny matchbox 
full of nutmeg had the kick of three or four reefers. 

A more recent but less accessible reference was a short article on page 22 
of the Chicago Sun-Times for March 3, 1961. It told of the dismissal of a 
Cook County Jail guard caught smuggling nutmeg and nose inhalers into 
the jail. 

An officer of the Federal Bureau of Prisons has written (18) : 

We are aware of the narcotic reaction these spices may have when improperly 
used, and, therefore, it is standard practice in the Federal prisons to maintain care- 
ful control of both items [i.e., nutmeg and mace]. Due to this control and also to the 



193 



fact . . . that few people are aware of their stupor-inducing powers, we have no 
problems with these items. I have read articles in various publications which imply 
that the use of nutmeg and mace is widespread in prisons. However I do not know 
of a single instance in the Federal Prison system where either spice was used by 
inmates for its narcotic effect. 

There is, hovrever, ample confirmation of this rumored use of nutmeg 
in a study conducted hj Weiss at the Xew Jersey State Prison at Trenton 
in 1960. Weiss wrote (i.9) : 

It is widely believed by inmates of correctional institutions that the drug action 
of nutmeg produces reactions similar to those of legally prohibited drugs which are 
considered habit-forming and addicting. Although its illicit application is most cer- 
tainly not widely known in the extra-mural setting, personal communications by 
prisoners are to the effect that it is used, not only in the community [i.e., the 
outside], but was also used in the armed forces in Europe in World "War II. 

Weiss studied ten male inmates of the prison, most of whom had had 
previous experiences with marihuana and other drugs. Six of them had 
learned of the use of nutmeg during their imprisonment ; the others had 
already known about it. The number of times these men had tried Myristica 
was impressive. One had taken nutmeg on 10 different occasions, one 30, 
one 52, and one 475. The minimum amount of ground nutmeg any man 
ingested was 2 to 3 tablespoonfuls, and one had once taken two cups of 
the spice as a single dose (apparently without untoward effects). The drug 
was always taken orally, usually stirred into hot liquids. 

Weiss noted no uniformity of time of onset of action, which ranged from 
10 minutes to four hours. Duration of action ranged from four to 24 hours. 
Most of the subjects compared nutmeg to marihuana, although some also 
likened it to heroin, and alcohol. Most experienced a sense of being trans- 
ported aloft, along with drowsiness in some cases and excitement in others. 
In all instances tliirst was increased, but himger was not stimulated. Ee- 
ported side effects included nausea, abdominal spasm, vomiting, constipa- 
tion, tachycardia, insomnia, and drowsiness. 

Two cases of acute brain syndrome, with psychotic reaction due to nutmeg intoxica- 
tion, were reported. Each of the two subjects had chronically ingested powdered 
nutmeg over a long period. . . . Aside from these cases of poisoning, the hallucino- 
genic effects rei)orted were transitory and of brief duration. 

Consumption of nutmeg was an important aspect of life in the prison. 
Weiss has added (20) : 

Inmates would carry little matchboxes in which they would store a supply of nut- 
meg (equivalent to one dose). They could then take the dose along with them to the 
shops in which they worked during the day. Users consider themselves to be more 
lively and cheerful. Thus, they feel they have dispelled their inner gloom. However, 
drug users seldom take nutmeg once they leave the prison since they consider its 
effects to be inferior to those of heroin or marihuana, whatever may be the similarity 
between them. 

Shortly after Weiss's article appeared, nutmeg was banned from the Xew 
Jersey State Prison kitchen. 

I have received information from several former prison inmates, sug- 
gesting the practice to be common. One correspondent writes : "During 16 
months in a Massachusetts correctional institution, I knew three individ- 



194 



uals who on occasion did use nutmeg as a snuff for 'kicks.' It was done on 
weekends and widely dispersed as to time." Another, from California, 
writes : "I can tell you that nutmeg is a commonly used high within prison 
walls — so much so that it is frequently locked up apart from the other 
normally used spices. . . . Convicts, because of the nature of their environ- 
ment, have rarely any alternative high." 

A final reference is this line from William Burroughs's Naked Lunch 
{21) : "Convicts and sailors sometimes have recourse to nutmeg. About 
a tablespoon is swallowed with water. Result vaguely similar to mari- 
huana with side effects of headache and nausea." 

Like prisoners, jazz musicians are said to have long used nutmeg as a 
substitute for other drugs, especially marihuana. Confirmation is hard to 
come by. The only clear reference I have been able to find is a 1962 bio- 
graphy of the late Charlie Parker, known as "Bird." The leader of the 
band in which Parker made his recording debut in 1942 is quoted as 
reminiscing {22) : 

Bird introduced this nutmeg to the guys. It was a cheap and legal high. You 
can take it in milk or Coca Cola. The grocer across the street came over to the club 
owner and said, "I know you do all this baking because I sell from 8 to 10 nutmegs 
a day." And the owner came back and looked at the bandstand and there was a 
whole pile of nutmeg boxes. 

To summarize thus far: The toxic properties of nutmeg have been 
recognized for hundreds of years, probably ever since the spice was first 
prescribed medicinally in large doses. Published reports of Mjj^ristica 
narcosis were most frequent around the turn of the last century when many 
women took nutmeg as an emmenagogue or abortifacient. Some evidence 
suggests that nutmeg may have long been used as an intoxicant in certain 
parts of Asia. In our century, for at least the past thirty years, prisoners, 
jazz musicians, sailors, and probably others have used nutmeg as a sub- 
stitute for marihuana or other drugs. They either eat or snuff it in variable 
amounts and commonly experience symptoms much more like those of 
the familiar hallucinogens than those described in the old reports of nut- 
meg poisoning. 

Use by Students 

In our own society the fastest-growing group of drug-takers is not the 
prison population or jazz world but rather students and "student-types." 
I do not care to add another guess to the many published estimates of what 
percentage of college youth experiments with hallucinogens. I will simply 
point out that most observers find that significant numbers of students now 
try marihuana and stronger drugs like LSD. It is especially noteworthy 
that many of these people would never have indulged in such activities 
even five years ago. I doubt, for example, that more than a handful of 
law students, medical students, or divinity students had experienced the 
effects of Cannabis before 1963, when hallucinogens first came to the full 
attention of the national press. But today many occasional marihuana 



195 



smokers come from these groups. Students have also been the initiators 
of drug fads in recent years. The flurry of excitement over morning-glory 
seeds in 1963 and 1964 Avas generated largely by college undergraduates 
and high school pupils. One would expect that nutmeg, because of its fre- 
quent use by other groups as an alternative hallucinogen, might also be 
included in the student's or beatnik's index of psychoactive substances. 

I have been particularly interested in this possibility because I first 
learned of Myristica's psychopharmacological potential through an invita- 
tion to a "mace party" given by several undergraduates at Haverford 
College near Philadelphia in 1961. The students said they and many of 
their classmates had been introduced to the spice by a visiting beatnik 
from Baltimore, who had sponsored several mace parties on campus. 

Only one case of this sort has appeared in the medical literature — 
Payne's report of 1963, mentioned earlier. His two students had gotten the 
idea of taking nutmeg from a "beatnik acquaintance," who told them it 
would provide "a mental state somewhat akin to ethanol intoxication with- 
out requiring the use of alcohol" {16). I have been able to find only one 
other published account — an article titled "Nutmeg Jag" in the sumimer, 
1964 issue of a University of Mississippi student magazine. It described 
a nutmeg party attended by eight persons. One participant — a young man 
who consumed a whole standard-size can of the ground spice (nearly 40 
g. or 1.5 oz.) — recalled afterward {23) : 

I felt as if I were in an echo chamber . . . my voice sounded vague and dis- 
tant ... it was like being drunk without the ordinary alcoholic effects. . . . Two 
friends of mine had told me about the 30-cents, three-day drunk they had after 
taking nutmeg, so I tried it out of sheer disbelief. 

Over the past six months I have been in touch with officials of student 
health services at representative universities throughout the countr^^ in an 
attempt to collect additional reports of Myristica intoxications. Signifi- 
cantly, most of the responding j)hysicians were unaware of nutmeg's non- 
culinary uses. Only two university clinics had cases on record. Dr. Henry 
B. Bruyn of the University of California at Berkeley student health serv- 
ice notes two instances of intoxication. In October, 1963, two days after 
an issue of the Ladies Home Journal appeared with a reference to nutmeg 
in a story on hallucinogenic drugs, a 20-year-old female student was ad- 
mitted to the hospital with a chief complaint of abdominal cramps. The 
night before she had taken 4 teaspoons of ground nutmeg because a friend 
had told her it would get her high. Her roommate joined her in this in- 
gestion. The next morning she awoke drowsy and fainted in the bath- 
room. Physical examination was normal except for orthostatic hypoten- 
sion, and she was recoA'ered the day after admission. She told a phj'sician 
she had taken the spice because she "felt she needed something to do." 

In January, 1965, a second female Berkeley student was admitted, age 
17, again with abdominal cramps. Four hours previously she ]iad eaten 
21/2 teaspoons of nutmeg because she had heard it would give her hallucina- 
tions. She, too, recovered quickly. 



196 



Dr. B. W. Murphy of the University of Maryland contributes one other 
case. He writes that he knows of a male student who induces dreamy 
hallucinatory states by ingesting a whole can of ground nutmeg. 

Does the scarcity of reported cases indicate a low frequency of nutmeg 
use by students? Probably not — just because students are reluctant to 
present themselves for medical treatment of drug intoxications, even when 
they suffer alarming symptoms. Relying solely on health services records, 
one would conclude that marihuana is also very little used by college 
students. 

To get a more accurate idea of the extent of experimentation with nut- 
meg on college campuses, I placed advertisements requesting information 
on the spice in several student newspapers and also interviewed students 
from many areas of the country. By these methods, I easily collected a 
number of accounts of nutmeg narcosis. I have selected some of these to 
illustrate typical patterns of use. 

Case #1 (college sophomore) — 

I heard about the effects of mace from a beatnik who visited our campus and induced 
students to "turn on" with two teaspoons of this spice stirred into fruit juice. I didn't 
try it at the time, but a few months later five of us held a mace party in my apartment. 
To the disappointment of all, we felt just the same three hours after drinking down the 
mace. Convinced that the alleged hallucinogenic properties of mace were imaginary, we 
separated and I went to bed. I remember feeling somewhat lightheaded and having 
vague stomach pains before falling asleep, but I had no other sjT)mtoms until I woke 
up the next morning with a splitting headache, a burning thirst, and malaise. I later 
learned the other four had felt much the same on arising. 

Case #2 (college juniors) — 

Five of us tried to get high by eating two whole nutmegs each. They are terrible 
things to try to chew up and swallow. We all had warm feelings in our stomachs im- 
mediately afterward and began sweating more than usual. One of us eventually had a 
pronounced reaction, but the rest of us noticed nothing unusual and gave up after two 
hours. The next morning we all had headaches, extreme dryness of mouth and throat, 
creaking joints and dizziness. 

One of us had a different experience. He went back to his room to read, and exactly 
four hours after taking the nutmeg he was suddenly overcome by a drowsiness so pro- 
found that he could hardly get up to turn off the light. As he fell into bed he had im- 
pressions of 'strange shapes floating' around him. He then sank into a heavy sleep. 
When he woke up seven hours later, he could barely move. He was very dizzy and 
staggered when he tried to walk ; also, he could not see clearly for several minutes. 
His mouth and throat were parched, and water did not relieve the dryness. Two hours 
after he got up he again became drowsy and "sank into a sort of trance state." At this 
time he had a vivid impression that he was floating with his limbs separated from 
his body. Eight hours later he was fully recovered. 

Case #3 (an ex-student in San Francisco) — 

I have had completely negative results from nutmeg, perhaps partly precipitated by 
the environment and definitely partly by the nauseating effects of the drug. I ate three 
ounces, which may well have been too much. About two hours later I drank four beers. 
Then about three-quarters of an hour after the beer I began noticing unusual effects. I 
was in an unfamiliar night club and started to become disoriented. I talked continuously 
and repetitively, but it seemed as though another person were talking. I seem to have 
been wandering around in a daze, unaware of my surroundings. I was then ejected 



197 



from the club. Paranoid delusions set in. I believed the owners of the club had drugged 
me. I forced my way back in, which resulted in my being jailed for drunk and disorderly 
conduct. The day I spent in jail was one of total confusion. In fact, it was a full day 
before I realized I was in jail. I was very belligerent, a condition apparently precipitated 
by the belief that I was going to be executed. I became ill and vomited. I imagined the 
other prisoners were Nazis who were guarding me. One day in jail finally restored my 
reason, and I was released. No hallucinations occurred as far as I can recall. 

Case #4 (college junior) — 

I drank one ounce of nutmeg in water. Four hours later I began feeling feverish and 
delirious. These sensations continued for several hours and left me with a bad hangover. 
I would not repeat the experience. 

Case #5 (21-year-old female secretary for a student newspaper) — 

I took one teaspoon of nutmeg in water after reading about it in Malcolm X's auto- 
biography. Nothing happened. 

Case #6 (college junior) — 

I took a whole can of nutmeg mixed with water. I had no effects at all from it. 
Case #7 (medical student) — 

When I was a junior in college at the University of Colorado, I got to know a group of 
nutmeg-takers because the leader of it had been a close high-school friend. In 1963, I 
went to his apartment for drinks, and he told me to take a matchboxful of ground nut- 
meg, packed into gelatin capsules. The method of these people was to take the nutmeg 
before they went to bed so that they would wake up high and avoid the nausea nutmeg 
often caused. Most said the effects were different from both morning-glory seeds and 
marihuana. Some experienced floating feelings. They took nutmeg occasionally for kicks, 
but did not attach too much importance to it. I do not know where they first learned of 
this habit, but my friend had worked as a volunteer in a prison before 1963 and may 
have been told about it there. 

Case #8 (college sophomore) — 

One evening my roommate and I each took a tablespoon of nutmeg in water after 
reading about it in Malcolm X's book. Nothing happened, so I went to bed. I woke up 
the next morning with incredible malaise and tachycardia. These symptoms eventually 
subsided but have recurred about once a week accompanied by severe anxiety for the 
past year. This reaction occurs spontaneously but also is brought on by eating anything 
containing more than a minute amount of nutmeg. One doctor has suggested that it may 
be an allergic reaction. My roommate had no effects except that he still cannot eat any- 
thing with nutmeg without experiencing an overpowering taste of the spice. 

Case #9 (college junior) — 

A friend told me about nutmeg and came over to show me how to do it. He mixed a 
drink of about half coffee and half nutmeg, which my roommate and I drank. Nothing 
happened to us in an hour, so we went to bed. Next morning I found myself on the 
floor with the worst hangover of my life. My roommate felt as bad. To this day neither 
of us can eat anything with nutmeg — we can't bear the taste. 

Case #10 (a 42-year-old Berkeley woman who describes herself as "ec- 
centric" with a "terrible fear of marihuana" and other drugs. After reading 
of nutmeg in a "manual of hallucinogenic drugs" she decided to try it since 
it was "cheap, legal, and available." She took nutmeg on several occasions and 
wrote extensively about her experiences. Here is one description.) — 

I drank about five grams of nutmeg in a glass of fruit juice at about 9 :30 a.m. An 
hour later I felt a surge of happiness when a freight train whistled. I closed my eyes 



198 



in search of hallucinations, bat none came. A certain diuretic effect and pungent scent 
in my urine were evidence that the drug had already taken effect. I read the morning 
paper until 11 :30 when there came a pleasant drowsiness. I closed my eyes and saw : 
silver spears of grass waving across an azure sky, silver waves of poplar trees swaying 
and dancing in the sun. I arose to walk and staggered. The light was flickering and dim 
as if I were partially blind, so I lay down on a couch in the kitchen. Closing my eyes 
again, I was overwhelmed by visions : golden spangles and rings of light on moving 
water, dancing moons and stars, everywhere a predominance of gold and silver 
images. . . . 

About 12 :30 I opened my eyes and noticed that the stove was far, far away ; the 
very walls had receded ; the kitchen was cathedral-like in its dimensions. I stood up to 
look at myself, and I was unusually tall. My feet were small and far away ; it was like 
looking through the wrong end of binoculars. I thought to myself, "This must be what 
marihuana is like." 

The effect continued several hours until she fell asleep. There were no 
aftereffects. 

Conclusions 

From these and other cases I draw the following conclusions : 

1. Significant numbers of students and persons living in student communi- 
ties attempt to induce hallucinations with Myristica. 

2. Unlike prisoners or musicians, who resort to nutmeg when their sup- 
plies of standard drugs are cut off, students often take nutmeg as a first 
experience before they try Cannabis or other substances. Nutmeg and mace 
are cheap, legal, and available at the nearest grocery store. 

3. Typically, the young nutmeg-eater first learns of the spice's psycho- 
activity from a friend or from a published reference. 

4. Doses range from one teaspoon to a whole can of ground nutmeg. Almost 
always, the spice is drunk in a glass of juice or water. 

5. Onset of action is commonly 2 to 5 or more hours after ingestion. Most 
neophytes are not aware of the delay. In a very common pattern of intoxica- 
tion, a person takes an adequate dose of nutmeg in the evening, goes to bed 
after several hours of waiting in vain for effects, and wakes up the next 
morning with many of the physical symptoms of toxicity : malaise, headache, 
dry mouth, tachycardia, dizziness. 

6. Some of the reported reactions to nutmeg must be purely psychological. 
A dose of one teaspoon is probably insufficient to cause true symptoms. 
Similarly, hallucinations or mental changes that come on within thirty min- 
utes of ingestion are likely to be factitious. 

7. Reactions to nutmeg vary from no mental changes at all to full-blown 
hallucinogenic experiences like those caused by hashish or LSD. There is no 
apparent correlation between dose and psychoactive effect. Might this ex- 
treme variability represent differences in pharmacological potency of differ- 
ent batches of nutmeg? Or do people vary greatly in their sensitivity to the 
active principle ? 

8. Visual hallucinations are rather less frequent with nutmeg than with 
drugs like LSD or mescaline, but distortions of time and space perception 



199 



with feelings of unreality are common, as with Cannabis. Sensations of float- 
ing, being transported aloft, or having one's limbs separated from the body 
are frequently reported. 

9. Effects of a single dose of nutmeg usually subside within 12 to 48 hours 
An intriguing aftereffect occasionally mentioned is persistent sensitization to 
the taste of the spice. 

10. Most young people who try nutmeg take it once or twice but do not use 
it habitually. Those who regularly smoke marihuana regard nutmeg as an 
inferior hallucinogen, largely because of the unpleasant side effects. 

11. Ignorance of the psychoactive properties of nutmeg is unquestionably 
the most important factor limiting extent of its use as a drug. 

I want to emphasize the last point. I began this general review by indicat- 
ing the differences between nutmeg and other hallucinogens. From a public 
health viewpoint, the crucial difference is that most persons in the country 
have not yet heard that nutmeg is intoxicating. Not only is nutmeg cheap, 
legal, and available, it is also familiar, which makes it seem safe and inviting 
to those looking for a first hallucinogenic experience. These considerations 
lead to one inference : as publicity is accorded the psychopharmacological 
properties of Myristica, use of nutmeg and mace as intoxicants will certainly 
increase. Hopefully, we will soon have the knowledge to determine the dan- 
gers and potential values of this modern use of an ancient spice. 

BIBLIOGRAPHY 

(1) Feegtjson, a. M. and J. Ferguson. "All About Spices." Colombo, Ceylon, 1889. 

(2) Ridley, Henrt N. "Spices." London, 1912. 

(3) Warburg O. "Die Muskatnuss." Leipzig, 1897. 

(4) "What You Should Know About Nutmeg and Mace." New York, American Spice 

Trade Association, 1966. 

(5) Redgrove, H. Stanley. "Spices and Condiments." London, 1933. 

(6) U.S. Department of Commerce, Bureau of the Census figures complied by American 

Spice Trade Association, New York. 

(7) Guenther, E. "The Essential Oils." New York, 1952. 

(8) "The Pharmacopoeia of the United States of America." XV, Easton, Pa., 1955. 

(9) Power, F. B. and A. H. Salway. "The constituents of the essential oil of nut- 

me;." J. Chem. Soc, 91 : 2037-2058, 1907. 
{10) Weil, Andrew T. "Nutmeg as a Narcotic." Econ. Bot., 19: 19^217, 1965. 

(11) Green, Robert C, Jr. "Nutmeg Poisoning." J. Amer. Med. Assoc., 171: 1342-1344, 

1959. 

(12) PuRKiNJE, J. E. "Einige Beitraege zur physiologischen Pharmakologie." Neue 

Breslauer Sammlungen aus dem Gebiete der Heilkunde. 1 : 423-443, 1829 ; 
quoted in Hanzlik, "P. J. Purkinje's pioneer self-experiments in psychopharma- 
cology." Calif, and Western Med., 49 : July and Aug., 1938. 

(13) Watson, G. C. "Symptoms of poisoning after eating a quantity of mace." Prov. 

Med. Surg. J., Jan. 26, 1&48. 

(14) McCoRD, J. A. and L. P. Jeevey. "Nutmeg (myristicin) poisoning." J. S. Carolina 

Med. Assoc., 58 : 436-438, 1962. 

(15) CusHNY, A. R. "Nutmeg poisoning." Proc. Royal Soc. Med., 1908-1: 39. 

(16) Payne, Robert B. "Nutmeg intoxication." New Eng. J. Med., 269 : 36-38, 1963. 

(Mention of this article was made a few weeks later in the "Medicine" section 
of TIME Magazine.) 



200 



(17) X, Malcolm with Alex Haley. "The Autobiography of Malcolm X." New York, 

Grove Press, 1964. 

(18) Alldkedge, Noah L., Deputy Assistant Director, U.S. Bureau of Prisons. Per- 

sonal communication, April 6, 1964. 

(19) Weiss, George. "Hallucinogenic and narcotic-like effects of powdered myristica 

(nutmeg)." Psychiat. Quart., 34 : 346-356, 1960. 

(20) Weiss, George. Personal communication, April 18, 1964. 

(21) Burroughs, William. "Naked Lunch." New York, Grove Press, 1959. 

(22) Reisner, Robert George. "Bird: The Legend of Charlie Parker." New York, 

Citadel Press, 1962. 

(23) Andre, Sigeid. "Nutmeg jag." Mississippi Mag., 4: 18, 1964. 



262-016 0-67—15 



201 



The Chemistry and Psychopharma- 
cology of Nutmeg and of Several 
Related Phenylisopropylamines 

Alexander T. Shulgin 

Department of Pharmacology, University of California 
San Francisco Medical Center, San Francisco, California 

Thornton Sargent* and Claudia Naranjo 

Centro de Estudios de Antropologia Medica 
Universidad de Chile, Santiago, Chile 

Our report today has been divided into two separate portions. The discus- 
sion of nutmeg and its composition, and of the possible involvement of its 
chemical components. The psychotropic intoxication has a natural division 
into two areas of presentation. The first is a brief description of the plant ; a 
presentation of the methods and procedures for the isolation and the identifi- 
cation of the many components in the oil from the plant, and a careful defini- 
tion of those components that are most probably involved in the intoxicative 
syndrome. 

The extension of these components in to the corresponding amphetamines, 
their effectiveness in humans, and the likelihood of their being an acceptable 
explanation of the effects of the total nutmeg, will constitute the latter part 
of this report. In the previous paper there was presented some of the history of 
nutmeg, and a description of the style and extent of its usage in various cul- 
tures. In the reports that will follow, specific descriptions of the human syn- 
drome of intoxication, and some of the pharmacological ramifications of its 
study, will be presented. 

At this point we would like to present a factual description of the various 
chemical materials that have been found to make up the volatile (and pre- 
sumed active) fraction of nutmeg. On the hypothesis that one or more com- 
ponents may be appropriately assigned the responsible role for the nutmeg 
intoxication, there is a need for an exact chemical definition of nutmeg. But 
even before this, we must define in botanical terms just what is meant by the 
name nutmeg. 

Properly the nutmeg tree is any plant found in the Genus Myristica. Two 
species are known to be native to India. M. malabarica produces a seed some 
four centimeters long and elliptically shaped, and M. canarica produces a 
small spherical seed about two centimeters across. Both contain primarily 
fats and myristic acid, and being virtually without odor or volatile oil have 
achieved no position of importance. In the East Indies the seeds of M. suc- 
cedanea^ known as "Pala Maba" in the Indonesian areas, are also small and 
quite elongate in shape, but they have proven valuable as rich sources of the 
nutmeg essential oils. Another species, M. argentea, has actually been used 

•Present address : Donner Laboratory, University of CaHfornla, Berkeley, California. 



202 



in the spice trade under the name of "New Guinea Nutmegs" or "Long Nut- 
megs". However the quantity and quality of the volatiles from its seeds are 
quite low. The plant that has achieved the widest study and commercial 
exploitation, and which is the subject of this portion of this symposium, is M. 
fragrans. This species originated in the Mollucas and has been propagated 
throughout the adjoining Indonesian islands, giving rise to the so-called 
East Indian nutmeg of commerce. 

A little over a hundred years ago, the tree was introduced into the Carri- 
bean area and since the end of World War II has led to the establishment of 
a major industry. Grenada, of the windward islands, now supplies a major 
portion of the world's needs. The West Indian nutmeg is generally conceded as 
being of a somewhat lower quality than its East Indian forebears; the best 
grade of mace still comes from Asia. 

The tree has also been translocated into Ceylon, and much of the early 
analytical work on the composition of the natural extracts was conducted on 
nutmegs from this source. It is no longer possible to obtain commercial sam- 
ples with this designation however, and it must be assumed that any product 
from this area has been absorbed into the East Indian category. 

The three areas of the plant M. fragrans that have received any analytical 
attention are the leaf, the arillode (which lies within the husk but outside 
of the shell of the seed, and which is known as mace) , and the kernel of the 
seed itself, the nutmeg. The leaves have received only a cursory examination, 
which has indicated that although there is only a small amount of steam- 
distillable material present (about 1.5% of the dry weight) its composition 
is substantially the same as that of the plant parts associated with the seed 
{1). The studies that concern the volatile oils of mace are best presented 
later in direct comparison with the analysis of nutmeg itself. As it is only the 
nutmegs that are invested with the reputation of psychotropic efficacy, they 
have served as the primary focal point of our analysis. 

The actual nutmeg, when removed from its hard brown shell or testa is a 
spherical kernel that weighs about five grams. The thorough work of Power 
and Salway {^) must serve as a definitive study of the composition of the 
entire nutmeg. There are two classical ways of extracting the potentially 
interesting materials from the whole fruit. 

Figure 1 shows the approximate distribution to be expected with the em- 
ployment of these methods. The process of expression, or the extraction with 
an organic solvent, provides about a third of the total original weight. This 
fraction is known as the fixed oils, and has also been called Nutmeg Butter 
or "Oleum Myristicae expressum". This fraction is substantially free of vola- 
tiles, and is composed primarily of triglycerides. Myristic acid is the prin- 
ciple compound here, although both oleic acid and linoleic acid are also 
found. This fraction has been used as a source of trimyristin {3). The small 
non-fat remainder is composed of unsaponifiable compounds, primarily oxy- 
genated polyterpenes and phytosterols. 

The subjection of the total crushed seed to distillation with live steam 
removes some 10 to 15% of the weight, known as the volatile oil fraction. 
The small overlap that is shown with the expression fraction is due to the 



203 



CHEMICAL GROUP DISTRIBUTION IN NUTMEG 



FIXED OILS 

25- 40 7o 

(NUTMEG BUTTER) 

O 
Ijj 


— ^""'^'^^ UNKNOWN 

>v OTHER GLYCERIDES 

1 TRIMYRISTIN 


•s. 


^"-.^FATTY ACIDS 


i 8-15% VOLATILE OILS 


' ^^"-^ AROMATICS 

80% ^ 

1 TERRENES 


UJ 

_l 
o 

X 

^ 45 - 607o PULP 


INERT 



Fig. 1 



fact that some of the volatile components are removed in the solvent extrac- 
tion and are held tightly by the fixed components present. This volatile frac- 
tion is composed primarily of terpenes, which make up some 80% of its total 
weight. The remainder is the aromatic fraction, composed of ethers and 
phenolic bodies. 

The residue that remains after the expression of the solubles and the dis- 
tillation of the volatiles constitutes some 50% of the original mass of the 
nutmeg. It is presumably a cellulose-like pulp, and it remains totally unex- 
plored as far as any chemical analysis is concerned. 

It must be stated here, in anticipation of later discussions on the pharma- 
cology of nutmeg, that no definitive evaluation of these fractions (fats and 
pulp) have been made. It has, however, been generally accepted that it is the 
volatile oil fraction to which one must look for the effective agents of nutmeg, 
and it is this "Oil of Nutmeg" that has been admitted to the U.S. Pharmaco- 
peia as a medicinal. This oil comprises between an eighth and a twelfth of 
the entire fruit, and it serves as the object of the present study. 

An exacting analysis of this volatile fraction has been performed. To this 
end a five pound sample of West Indian Oil of Nutmeg (from the George 
Lueders Company, New York) was subjected to fractional distillation em- 
ploying a 70 tray Oldershaw column. Fractions were collected in a continuous 
sequence and each of these was in turn analysed and further fractionated 
employing a preparative gas liquid chromatographic procedure. Identity of 
each component was established by direct isolation, (employing a Varian 
A-700 Autoprep) and spectral comparison to reference samples (through 
infra-red and high resolution mass spectroscopy). Quantitative measure- 
ments were achieved employing a Varian Aerographer 1200 with a flame 
detector, and peak areas were established with an Aerograph 475 Integration 
System. 



204 



TOPOGRAPHICAL REPRESENTATION OF OIL OF NUTMEG 




£a JO *e> j-o 

''O' S>0' //O' /JO' /J-o' 7~^/^/'C/>/!l7-C/!C 



c///'?o/V/^ri:^<:^/v^/='/^/' 
Fig. 2 

Figure 2 shows what might well be called a fingerprint of the oil of nutmeg. 
On the z-axis is shown the results of the distillation. This was continued on 
the 70 tray column at 15 mm/Hg until the aromatic fraction was reached. 
Then the distillation was completed at 1 mm/Hg through a shorter column. 
Although the actual fractions collected were not exactly of 25 grams as is 
presented in the figure, the weights have been normalized to this amount, 
and each horizontal line thus represents an equal weight of distillate. 

The X-axis represents the progress of gas liquid chromatographic separa- 
tion. The time required for desorbtion of each of the peaks is shown, and as 
the system has been programmed for a rise of 2°/min., this also represents 
the temperature of desorbtion. 

The y-axis is peak height and, as it is characteristic of temperature pro- 
grammed GLC spectra to display a constant peak half-width, this height 
is proportional to peak area. 

Several peaks (components) are obvious that would be superimposed by 
one of the techniques alone (GLC or distillation), but are readily separated 
by applying the other. 

The long ridge down the left hand side of the presentation, parallel to 
the z-axis, represents the similar terpenes a-pinene, sabinine, and dipentene, 
and this is separated in a natural division from the second and smaller group, 
the aromatics. 

The preponderance of a-pinene has been mentioned, but both sabinine and 
y-terpinene (1, i-menthadiene) warrant special note as neither has been 
observed in nutmeg before. The terpenyl alcohols have been included in this 



205 



group as are the two aromatic hydrocarbons cymene and the previously 
undetected toluene. On the other hand both cineole and camphor have been 
recently reported to be present to the extent of a percent or two, and citro- 
nellol and citronellal have been reported in trace amounts (4) ; none of these 
were present in the sample we investigated. d-Borneol, Avhich had originally 
been assigned to nutmeg on indirect evidence (5) was not present in our 
sample. 

The second and smaller group, the aromatic ether fraction, is the more 
interesting and as will be shown later is the more likely to be implicated in 
the psychopharmacology of nutmeg. In Table I are shown the nine aro- 
matics that have definitely been established as being present in nutmeg, and it 
also shows the extent of their contribution to the sample analysed. 

The three major components, myristicin, elemicin, and safrole constitute 
nearly 9/10 of the group. In the previously reported studies of nutmeg, 
myristicin has always been recognized as a major component, and has thus 
often been thought to be responsible for the psychopharmacological activity 
of the total extract. In the thorough study conducted on the Ceylonese Oil of 
Nutmeg (J) safrole was found only in very small quantities, but recently its 
identity as a significant component of East Indian oils has been reported, 
(6) although it appeared to be absent in the West Indian varieties. 

COMPOSITION OF OIL OF NUTMEG 
LUEDERS WEST INDIAN 



TERPENIC FRACTION 


% 


AROMATIC FRACTION 


% 


o-PINENE 


36.16 


SAFROLE 


1.29 


/9-PINENE 


6.16 


METHYLEUGENOL 


0.62 


CAMPHENE 


2.97 


EUGENOL 


0.17 


SABINENE 


12.75 


METHYLISOEUGENOL 


0.36 


1,4-p-MENTHADIENE 


3.47 


ISOEUGENOL 


0.19 


l,4(8)-p-MENTHADIENE 


1.12 


MYRISTICIN 


7.04 


1,8-p-MENTHADIENE 


12.78 


ELEMICIN 


2.36 


TOLUENE 


0.10 


ISOELEMICIN 


0.1! 


p- CYMENE 


1.82 


METHOXYEUGENOL 


0.25 


I-MENTHENE-4-0L 
I-MENTHENE-8-0L 


2.93 
0.4! 


OTHERS 




LINALOOL 


0.15 


MYRISTIC ACID 


2.87 


6ERANYL ACETATE 


0.20 


UNIDENTIFIED 


3.72 



Table I. 



206 



DISTRIBUTION OF THE PRINCIPLE AROMATICS IN 
VARIOUS MYRISTICA OILS 

L. Wl, F. W.I. L. E.I. F. E.I. D. ? L. ? F, E.I. D. ? 
NUTMEG NUTMEG NUTMEG NUTMEG NUTMEG MACE MACE MACE 



CH2CH=CH2 
^■t!?0 ' SAFROLE 



1.29 1.43 1.09 2.69 1.38 0 53 3 42 1 41 



CH3O 

^4/ \cH2CH=CH2 7.04 5.58 8.08 8 48 5.62 3 86 12.78 5.53 

''■y?0 MYRISTICIN 

CH3O 

CH30-/^^CH2CH=CH2 ^ '^^ ° ° °" ^ °^ ° °^ ° 

CH30^^'^ ELEMICIN 

X OF TOTAL OIL THAT 

IS AROMATIC 12 7 7 5 10 7 12 5 8 2 7.2 18 2 8.1 
•X OF TOTAL AROMATIC 

THAT IS ACCOUNTED 8 4 94 9 0 9 0 9 4 9 0 89 9 5 
FOR ABOVE 

Table II. 



We have made a comparative study of the aromatic fraction of several 
samples of Oil of Nutmeg from different geographical origins, and of Oil of 
Mace as well. These results are shown in Table II. Here the surprisingly wide 
variation that can occur between these principle components is apparent. The 
single consistent item is the presence of myristicin as a major component. In 
the figure the F found at the heads of the columns represents the source, 
Fritzsche Bros., New York. Similarly, L stands for Lueders Co. and D for 
Dreyers Co. The WI represents West Indian sources, and EI East Indian. 
The question marks refer to samples whose origin was undesignated. Safrole 
has been found in both East and West Indian oils and appears, in this 
analysis, to be present in an amount from 15-30% of the myristicin present. 
The amount of elemicin present is most erratic. It has been found to vary 
from over 2% in the Lueders West Indian Oil of Nutmeg, to only trace 
amounts in the Fritzsche samples. The various oils of mace show neither 
consistency nor correlation with the nutmeg samples, except that again, 
myristicin appears as the principle component. 

The assignment of the chemical structures of these compounds is a direct 
and simple matter when compared to the task of assigning responsibility for 
the intoxicating and psychotropic properties of nutmeg. The kernel itself is 
the only component of the tree that is invested with the reputation for 
biological activity. Further, it may be asserted that the psychoactive com- 
pound or compounds probably reside in the volitale oil fraction of the nut- 
meg, for this fraction has been shown in animal toxicology studies to carry 
the effectiveness of the entire seed. Human experiments Avith ground nutmeg- 
depleted of its volatiles have failed to show psychopharmacological responses 
(7). 



207 



With the satisfactory assignment of the identities of the various conspicu- 
ous components to be found in nutmeg, one must examine how each of these 
individually, or more likely in concert, may achieve a role in a reasonable 
explanation of the activity of the entire seed. Here there are two groups of 
compounds to consider, the terpenes and the aromatic eithers. It is tempting 
to dismiss the terpenes out of hand. Although they constitute by far the 
larger portion of the volatile fraction, the terpene hydrocarbons are generally 
held to be of biological effectiveness mainly as irritants. Turpentine has a 
composition quite similar in make-up to this terpene fraction; it has been 
widely used in many home remedies, but it has certainly not commanded 
reputation as an intoxicant. It may, however, have some function in assisting 
in the absorption of the various aromatic compounds through the gut. 

The aromatic fraction, then, would seem to be the most likely source of 
the psychotropic activity of nutmeg. Table III shows the structure of each of 
the compounds we have found in the aromatic fraction. Also shown is the 
amount in milligrams of each of these components that would be present in 20 
g. of the whole nutmeg, 20 g. being assumed to be that required to produce 



AROMATIC FRACTION OF OIL OF NUTMEG 



STRUCTURE 



NAME 



AMOUNT TO BE FOUND IN 
20 GRAMS TOTAL NUTMEG 
(IN MILLIGRAMS) 



H2c;-o 



CH3O 
CH3O 

HO 
CH3O 



CH2CH=CH2 



CH2CH=CH2 



CH2CH=CH2 



CH30-(^ y-CH=CHCH3 
CH3O 



CH-,0-f 



HO 

CH30' 

H 2(^-0 
CH3O 
^3 

CH30 

CH30/ 

CH3O 

CH3O 



CH=CHCH3 



CH2CH=CH2 



CH2CH=CH2 



CH=CHCH3 



CH2CH=CH2 



SAFROLE 



METHYLEUGENOL 



EUGENOL 



METHYLISOEUGENOL 



ISOEUGENOL 



MYRISTICIN 



ELEMICIN 



ISOELEMICIN 



METHOXYEUGENOL 



39 



18 



210 



70 



Table III. 



208 



psychotropic effects. As stated earlier, saf role, myristicin, and elemicin ac- 
count for some 84% of the aromatic fraction, and thus are the primary 
materials that we will consider. The possibility must always be kept in mind 
that one of the minor components could have an unusually high potency and 
thus contribute to the activity. 

Of the primary constitutents, myristicin is by far the most abundant, and 
for this reason was tested specifically for psychotropic activity by Truitt, 
et al (7). Doses of 400 mg. myristicin, almost twice the amount present in 
20 g. of typical nutmeg, were given to human volunteers and the observed 
symptoms were at least suggestive of psychotropic effects in 6 out of 10 
subjects. It will be seen later that those effects which might be expected from 
myristicin may be rather subtle, and so may require some synergistic activity 
of some of the other aromatic compounds to produce the full nutmeg 
syndrome. 

Saf role is also a component of other natural oils and spices, the most notable 
being the Oil of Sassafras which contains some 80%. Both the oil and the 
derived sassafras tea have enjoyed wide use, modestly as a flavoring, and in 
larger amounts as an internal medicament ; yet neither has a reputation for 
psychotropic activity as does nutmeg. 

Elemicin is unusual in that among the flavoring oils and spices, it occurs 
in appreciable amounts only in nutmeg. Further, as mentioned earlier, even 
in nutmeg the amount of elemicin is highly variable and depends upon the 
source of the extract. It also occurs in several obscure essential oils, none of 
which have been reported to have been used pharmacologically. It is, further, 
not separable from myristicin by fractional distillation. The myristicin em- 
ployed in all earlier pharmacology (including the human studies mentioned) 
was obtained by distillation from oil of nutmeg, and was taken to be the single 
substance myristicin. It thus may or may not have contained elemicin as well, 
depending on the origin of the oil. The variability of elemicin may account for 
the apparently highly variable degree of reported psychoactive effects of 
nutmeg, which in turn implies that elemicin may indeed be an active com- 
ponent. Of the aromatic components present in lesser amounts, only eugenol 
and isoeugenol have found use either as flavoring agents or as medicinals. 
They comprise about 80% of the Oil of Cloves for example, but again search 
of the literature on such natural products for some reputation for abuse as 
an intoxicant has been futile. 

There are thus several possibilities by which one or more of the aromatic 
components might be implicated as psychotropic agents ; 

1. One of the compounds that is present only in very small amounts may 
have unusually high potency, 

2. Elemicin may be a maj or contributor of activity, or 

3. A combination of two or more of the aromatics present may be involved. 
The three most abundant ones, myristicin, elemicin and safrole may be suffi- 
cient to account for the total activity. 

It is worth noting that nutmeg is the only plant source within which these 
three compounds have been reported as occuring together in any appreciable 



209 



quantity, and as will be seen later, each may contribute slightly different 
aspects to the total psychotropic effect. 

With the exception of myristicin none of the individual components of the 
aromatic fraction have been evaluated specifically as to their psychological 
effects. The ring substitution patterns of these compounds are notable in that 
several of them, specifically myristicin, elemicin and safrole, are identical to 
the ring structures of materials of established psychotogenic activity. The 
allylic side chain is amenable to chemical modification, as shown is Fig. 3, 
wliich could convert the naturally occuring compounds into ones of known 
psychotropic activity. It has been suggested {8) that the in vivo addition 
of ammonia to the olefinic site in either the allyl or the propenyl isomer would 
yield amphetamines directly. To speak of amphetamines as a chemical class 
is not strictly correct, but we use it to refer to variously methoxylated phenyl- 
isopropylamines. The "EO" in the figure indicates the presence of any variety 
of ether groups on the ring, and thus would include all of the aromatic 
ethers in the oil of nutmeg and in many other natural oils as well. The pos- 
sible mechanisms of such an in vivo transformation have been elaborated 
upon, and are plausible to the extent that each of the reactions has been 
achieved in vitro. Support for this transformation occurring in vivo has been 
obtained by Barfknecht (9), who found evidence for the production of 
amphetamine in rats after feeding them allylbenzene. This corresponds to 
ammonia addition in Fig. 3 without the "RO" ether groups. 

CONVERSION OF AROMATIC ESSENTIAL ETHERS 
TO ALKOXYAMPHETAMINES 




Fig. 3. 



210 



Throughout the general area of spices and of essential oils from plant 
sources there is about a score of substituted phenylpropenes, all of which 
are characterized by ring substitution of either methoxy groups or a methyl- 
enedioxy group (or both) and by the allyl or the propenyl side chain men- 
tioned above. Of these a total of eleven different ring substitution patterns 
have been reported as occuring ; the balance of the twenty known aromatics 
consists of isomeric variations of the side chain. The addition of an amine 
to this olefinic system might be extremely sensitive to substitutions near it, 
that is, whether the side chain be allyl, c/«-propenyl or ^mn^-propenyl. 
It may thus be in turn a determining factor in the psychotropic activity of 
any such substance under consideration. 

In the preparation for the study of this possible in vivo amination of 
these ring- substituted natural oils, a series of amphetamines that would be 
the result of such an addition has been completed. These are tabulated in 
Table IV, showing the principle natural source of each of the natural oils, the 
common name as they occur in the allyl (A) or propenyl (P) form, the 
orientation of the ring substituents, the code letter abbreviation of the result- 
ing base, the cogent physical and chemical data, and the potency of the 
compound in mescaline units. The latter measure is defined as the quotient 
of the effective dose of mescaline (assumed to be 3.75 mg/Kg as the base) 
divided by the effective dose of the substance in question, as determined by 
human titration. This ratio permits a direct comparison of relative potencies, 
based on mescaline equaling one. Mescaline has a ring substitution pattern 
identical with number 6, TMA, except that the side chain has only two 
carbons instead of three. 

It will be noted that several of the possible amphetamine derivatives of 
the components of the aromatic fraction of nutmeg do not appear here: 

AMPHETAMINES RELATED TO THE NATURAL ESSENTIAL OILS 

C \cH2CHNH2- HCl 
R0^^=/ CH3 



COMMON 
NAME 



PRINCIPLE 
SOURCE 



RING ORIENTATION 



SYNTHETIC 

CODE ROUTE M.RVC. mC POTENCY 

MESCALINE ■! 



1. 


ESTRAGOLE (A| 


0 OF 


ANISE 


4-OCH3 


MA 


A 


211 


60 


? 


2. 


NOTHOSMYRNOL 


(P) Q OF 


N.JAPANICUM 


2,4-(OCH3) 


2,4 DMA 


A 


147 


90 


? 


3. 


METHYLEUGENOL (A) 0 OF 


CITRONELLA 


3,4-(OCH3) 


DMA 


A 


147 


76 


7 


4. 


SAFROLE (A) 


0 OF 


SASSAFRAS 


3,4-(OCH20) 


MDA 


A 


186 


29 


2 


5. 


ASARONE (P) 


0, OF 


CALAMUS 


2,4,5-(OCH3) 


TMA-2 


B 


161 


60 


It 


6. 


ELEMICIN (A) 


0 OF 


ElEMI 


3,4,5-(OCH3) 


TMA 


A 


209 


63 


2 


7. 


CROWEACIN (A) 


0. OF 


E. CROWEI 


2-OCH3-3,4-(OCH20) 


MMDA-So 


A 


154 


59 


18 


«. 


MYRISTICIN (A) 


0. OF 


NUTMEG 


3-0CH3-4,5-(0CH20) 


MMDA 


B 


191 


60 


3 


9. 


(A) 


0 OF 


PARSLEY SEED 


2,3,4,5-(OCH3)4 


T.tro MA 


C 


136 


13 


7 


10. 


DILLAPIOLE (A) 


0. OF 


OILL 


2,3-(OCH3)2-4,S-(OCH20) 


DMMDA-2 


C 


130 


94 


? 


IL 


APIOLE (A) 


0. OF 


PARSLEY SEED 


2,5-(OCH3)2-3,4-(OCH20) 


DM MDA 


B 


175 


64 


? 



A< ^ BENZALDEHVDE, NITROETHANE, LiAIH^. 

&i CLAISEN (tE ARRANGEMENT, METHYLATION, ISOMERIZATION. CINOJ., LiAlH.. 

Ci ^ NATURAL ALLYL COMPOUND, ISOMERIZATION, C(NOj]^, LiAIH^. 



Table IV. 



211 



namely those which contain an OH substituent in addition to the methoxyl 
groups. These comprise some 5% of the aromatic fraction, and still remain 
to be explored in the human subject, either as purified components them- 
selves, or as their amphetamine extensions. Should the free hydroxyl group 
of any of these several materials confer an unusually high psychotropic 
potency on any of these compounds or on the corresponding amphetamines, 
this would contribute to the nutmeg intoxication beyond the explanations 
considered here. Eugenol itself has had some known medical uses however, 
and it would seem reasonable to expect that its psychotropic activity would 
have been noted had it existed. 

Published detail has appeared on the psychotropic effects in normal human 
subjects for the four compounds that are trisubstituted, numbers 5, 6, 7 and 
8 {10) . In every case the compounds had a greater potency than that of the 
reference substance mescaline. 

The base that corresponds to safrole, number 4, is 3,4-methylenedioxyam- 
phetamine, or MDA. This was first described pharmacologically by Gordon 
Alles {11) who reported visual effects at some 120 mg. Subsequent experi- 
ence {12) on a more extensive number of subjects has shown modest, if any, 
distortion or change of either visual or auditory perception, but rather a 
pronounced increase in emotional effect, which has proved to be of consid- 
erable value in psychotherapy. 

The base that would be the result of the addition of anunonia to myristicin, 
number 8, is 3-methoxy-4,5-methylenedioxyamphetamine, or MMDA. A 
complete description of the animal and human pharmacology and psycho- 
pharmacology of this compound is forthcoming {13). With regard to the 
work mentioned earlier in which 400 mg. of myristicin was tested in human 
subjects, the experience with MMDA indicates that the effects although 
identifiable in a psychotherapeutic setting, or in subjects trained to identify 
psychotropic effects, are rather subtle and may not have been detected by 
the psychological tests used in the study. The psychotropic effects of MMDA 
are rather similar to those of MDA, but in addition some 30% of the sub- 
jects reported rather vivid and well structured visual images appearing 
when the eyes are closed, although there are virtually no changes in eyes-open 
perception. The possibility that myristicin in the amounts present in nutmeg 
may contribute to the total effects of nutmeg, cannot at this point be 
discarded. 

The base that corresponds to number 6 is 3,4,5-trimethoxyamphetamine, 
TMA. This has been known as a psychotropic agent for some time (1^, 10a) . 
It has variously been described as having potent hallucinatory effects and 
as leading to apparently hostile reactions. More extensive appraisal of this 
compound in psychotherapeutic settings has confirmed the eyes-opened dis- 
tortions and occasional hallucinatory phenomena, and strongly suggests that 
its characteristic property is one of causing projection, in the psychological 
sense, by the subject. This can produce visual distortions, delusions (altera- 
tions in social perceptions), and sometimes apparently hostile projections 
which, however, have never led to any overt actions. 



2X2 



The analogous bases that correspond to the eugenols have not yet been 
evaluated, and as mentioned earlier represent another group of compounds 
that could contribute to the activity of nutmeg. 

There are two ways in which further investigations might be pursued; 
namely human evaluation of the individual compounds of the aromatic 
fraction of the oil of nutmeg, preferably synthetically derived to avoid con- 
tamination, and secondly, the further evaluation of the effects of the amine 
derivitives. It is entirely possible that the combination of the amines deriv- 
able from the essential oil aromatics could produce the psychological effects 
of nutmeg, while the clearly toxic effects could be due to the terpene frac- 
tion. Human evaluation of a mixture of these amines, in the proportions 
found in nutmeg, would explore the possibility of any synergistic amplifica- 
tion of the activity of these compounds. A corollary study would involve 
the chemical investigation of the metabolic fate of both the essential oils and 
the derived amines, on administration to human subjects, and may clarify 
whether or not these oils are in fact converted to amines in vivo. From the 
results of these studies, it is hoped that the interrelationship between the 
complex composition, and the yet more complex psychopharmacological struc- 
ture of nutmeg, can be resolved. 

REFERENCES 

(1) "Essential Oil from the Leaves of Nutmeg (Myristica fragrans Houtt.)", Th. M. 

Meyer. Ing. Nederland.-Indie 8 No. 1 VH 7-8 (1941). (CA 35 : 4549*). 

(2) "The Constituents of the Expressed Oil of Nutmeg", F. B. Power and A. H. Sal- 

way, J. Chem. Soc, 93: 1653 (1908). 

(3) "Trimyristin", O. D. Beal, Org. Syn., Coll. Vol. I., Second Edition p. 538 (1941). 

(4) "Application of Gas Chromatography to a Study of Nutmeg Oil Flavor", G. D. Lee, 

F. L. KaufEman, J. W. Harlan and W. Niezabitowski, Intern. Gas Chrom. Symp., 
I.S.A. Proc. 301 (1961). 

(5) "The Constituents of the Essential Oil of Nutmeg", F. B. Power and A. W. Salway, 

J. Chem. Soc, 91 : 2037 (1907). 

(6) "Gas Chromatographic Analysis of Oil of Nutmeg", E. A. Bejnarowicz and E. F. 

Kirch, J. Pharm. Sci., 53 : 988 (1963) . 

(7) "The Pharmacology of Myristicin, A Contribution to the Psychopharmacology of 

Nutmeg", E. B. Truitt, Jr., E. Callaway III, M. C. Braude, and J. C. Krantz, Jr., 
J. Neuropsych. 2 : 205 (1961) . 

(8) "Possible Implication of Myristicin as a Psychotropic Substance", A. T. Shulgin, 

Nature 210 : 380 (1966). 
(5) C. F. Barfknecht, University of Idaho (personal communication). 
{10) a. "The Psychotomimetic Properties of 3,4,5-Trimethoxyamphetamine", A. T. 
Shulgin, S. Bunnell and T. Sargent, Nature, 189: 1011 (1961) ; 6. "3-Methoxy-4, 
5-Methylenedioxyamphetamine, a New Psychotomimetic Agent", A. T. Shulgin, 
Nature 201: 1120 (1964); c. "Psychotomimetic Amphetamines; Methoxy 3,4- 
dialkoxyamphetamines", Experientia 20 : 366 (1964). 

(11) "Some Relations between Chemical Structures and Physiological Action of Mes- 

caline and Belated Compounds." G. A. AUes, in Neuropharmacology, The Josiah 
Macy Jr. Foundation, Madison Printing Co., Inc., 1959. 

(12) "The Psychological Effects of 3,4-Methylenedioxyamphetamine (MDA) Intoxi- 

cation." C. Naranjo, T. Sargent and A. T. Shulgin (in preparation). 



213 



"The Chemistry and Pharmacology of 3-Methosy-4,5-methyleiiedioxyamphetamrne 
(MMDA)." A Monograph. C. Xaranjo, T. Sargent and A. T. Shnlgin (in 
preparation ) . 

{14) "A New Hallucinogen : 3,4.5-Trimethoxyphenyl-(3-aminopropane, with notes on the 
stroboscopic phenomenon." D. I. Peretz. J. R. Smythies and W. C. Gibson. J. 
Mental Sci., 101: 316 (1955). 



214 



The Pharmacology of Myristicin 
and Nutmeg 

Edward B. Truitt, Jr. 

Battelle Memorial Institute, Columbus, Ohio 

The long history of observations concerning the pronounced psychotropic 
effect of Myristica fragrans (nutmeg) has not gone unnoticed by many dis- 
tinguished investigators, including some famous pharmacologists. A central 
problem in the pharmacology of nutmeg has been identification of the active 
component of the crude drug. As early as 1676, van Leeuwenhoek, the origi- 
nal microscopist noted that a volatile component which evolved from pieces 
of nutmeg in a glass tube repelled or killed mites. {1) Although Warburg, 
as late as 1897, still expressed doubt {^) it was clear by then that the volatile 
fraction, the oil of nutmeg, was more toxic than the crude drug. The well- 
known English pharmacologist, Cushny, stated that the residue from which 
the volatile oil has been removed has no effect upon animals. {3) In our early 
studies at Maryland, we confirmed this observation by human testing of a 
steam-distilled residue and noted only gastrointestinal effects. (^) 

Another pharmacologist, George Wallace, used the highest distillate frac- 
tion (149°C, 14 mm), which he found to be the most active and easily ad- 
ministered component, and observed that the cat was the most susceptible 
species among the mammalia to the toxic action of the drug. (5) Both Wal- 
lace and, a year later, Jurss {6) correctly attributed the high toxicity to 
hepatic fatty degeneration, but the cat is also most sensitive to the central 
excitation, tremor, salivation, and stupor produced by oil of nutmeg. Sir 
Henry Dale in 1907 most clearly differentiated the primary psychotropic 
effect from the secondary hepatic coma causing death in cats. (7) AJthough 
he noted, as others had, that the oil required a higher myristicin amount 
than the crude drug in order to produce symptoms. Dale attributed this to 
absorption difficulties with the purified product. Power and Salway, re- 
examining the question in 1908, concurred that myristicin was probably re- 
sponsible for the central effect, but was unfavorable for absorption in the 
pure state. {8) 

Pharmacologic interest in nutmeg then subsided for more than 50 years, 
until renewed by the curiosity of Dr. John C. Krantz at the University of 
Maryland who was consulted by several former students encountering cases 
of nutmeg intoxication. {If) This study was conducted with a myristicin- 
containing fraction distilled from oil of nutmeg at 145-155°C and 15 mm 
Hg pressure. Subsequent gas-chromatographic studies by Shulgin have 
shown this to be a mixture of myristicin with elemicin and perhaps a small 
amount of methylisoeugenol. {9) 

Initial studies on the pharmacologic action of myristicin and nutmeg 
which were conducted at the University of Maryland sought to answer 



215 



a variety of questions. {4) Toxicity studies showed that the East Indian 
spice was more toxic than a West Indian product. Animal toxicity deter- 
minations before and after steam distillation also confirmed Cushny's origi- 
nal observation that the volatile fraction was more toxic than the residue (3) 
In planning for human administration of a dose of the myristicin-elemicin 
fraction amounting to 400 mg per subject, a chronic study in rats was con- 
ducted and showed no growth inhibition at a daily dose of 10 mg/kg. 

A stimulant effect of myristicin was demonstrated by a shortening effect 
of the oil fraction on barbiburate sleeping time. These data are shown in 
Table 1. 



Table 1. — The effect of myristicin on the sleeping time induced by phenobarbital in the rat 



Group 


Mean 
sleeping 
time 


Standard 
error 


p value 


Phenobarbital 120 mg/kg I. P 


162 min 


±5. 31 




Phenobarbital 120 mg/kg I. P. plus 100 mg/kg 








myristicin I. P _ _ 


144 min 


±2. 27 


<0. 01 



The intravenous injection of large doses in the order 50-76 mg/kg to 
dogs, monkeys, and cats confirmed the feline species toxicity and showed 
clearly that tranquilization of wildness is not produced in the jungle-bred 
monkey. It is of interest that the product was hypotensive in the dog as are 
other monamine oxidase inhibitors. These intravenous injections were sus- 
pensions of the oily substance in acacia solution. More recently a stable 
emulsion has been achieved having the following composition: 



Percent 

Myristicin 1.0 

Pluronic F-68 0.3 

Dextrose 4.2 

Ethyl alcohol 1.0 

Distilled water qs 100.0 



Using this formula, mice were injected into the dorsal tail vein with doses 
of 100 mg/kg. Within 1 to 2 minutes, loss of righting reflex and apparent 
sedation appeared. 

One contribution to the metabolism of myristicin has recently evolved 
from interest in its synergistic effect upon other insecticides. Casida and his 
associates have shown that the methlyenedioxy bridge is the initial point of 
metabolic attack by hepatic microsomes and requires NADPHo (10). 
This reaction is shown in Figure 1. This metabolic transformation increases 
the chemical similarity of myristicin to the catecholamines. 

The structural resemblences of myristicin to mescaline and epinephrine 
prompted studies directed at measuring competitive inhibition of myristicin 
to other monoamine oxidase substrates. The method of Tedeschi et al, (11) 
was employed for estimation of monoamine oxidase (MAO) inhibition by 
potentiation of the central convulsant action of tryptamine HCl. A 0.5% 



216 



/ 




CH2— CH— 



microsomes 



NAIPH2 




CH2-CH=CH2 



H 




0 



■i> HCOOH + 




* 



HO 




/ 



H 



,14 



* C-"^ labeled 

Fig. 1. — Major metabolic pathway for methylene dioxyphenyl labeled myristicin in 
liver microsomal systems of the mouse. (Modified from Casida, et al. (10).) 

solution was injected intravenously into 10 mice per dose level. Three seconds 
or more of clonic jerking, tremors, and/or side-to-side head movements were 
the endpoint criteria used to calculate the CD 50 from dose-response lines by 
the method of Eubin et al. (13) in rats, scoring both eyes on a 5-point scale. 
Cerebral 6-hydroxytryptamine was measured by the Mead and Finger modi- 
fication {14-) of the method of Bogdanski et al. (15) 



No apparent effect was evident from the drug vehicles on the CD 50 of 
tryptamine (Table 2). When given orally 18 hours in advance. East Indian 
ground nutmeg gave some evidence of tryptamine potentiation (Figure 2). 
The optimum dose was 500 mg/kg. However, a much larger dose, 1000 
mg/kg showed reversal of the activity. 

Several samples of synthetic myristicin ^ were tested by the tryptamine po- 
tentiation test 18 hours after their oral administration. These results are 
shown in Figure 3. Both of these preparations showed considerable activity 
when the sample was fresh and lemon yellow in color. Later tests (not shown) 
after the liquid had turned to a light amber color consistently showed a con- 
siderable decline in tryptamine potentiation. These deteriorated solutions 
when studied by gas chromatography showed the appearance of an unknown 
component in addition to the myristicin. 

Tlie distilled concentrate of oil of nutmeg was much less active than the 
synthetic myristicin and, like ground nutmeg, reversed its activity with a 

1 Synthetic myristicin was kindly made available by Dr. Carl D. Lunsford, A. H. Robins Company, 
Richmond, Virginia. 



Results 



262-016 0-67— 16 



217 



I 



Table 2. — Tryptamine convulsion test for monoamine oxidase inhibition inv^o Summary 

of control tests 



Species 


No. 


Vehicle-18 hr 
prior, cc/kg 


CD50, 
mg/kg 


95 'J, confi- 
denct limits, 
mg,'kg 






N^one 


. yj 


1 0 . 4— 4U . 0 


( I 


21 


u 


17.3 


12.1-24.7 


I i 


28 


Liq. pet. 


24.5 


19.9-30.1 


it 


38 




28.0 


18.4-42.6 


tc 


37 


Acacia-2% 


25.8 


18.3-36.3 


Avg 


164 




25.0 


21.6-29.0 


Rat 


54 


None 


18.6 


13.6-25.5 




LOG DOSE - TRYPTAMINE, mg./kg. 

Fig. 2. — Effect of ground nutmeg on tryptamine convulsive threshold in mice when 

given orally in acacia suspension 18 hr before test: X X Control, CD50 mg/kg 

(±95% confidence limits) 25.0 (15.2-41.0); Q 200 O 200 mg/kg nutmeg, 20.0 

(14.2-28.2); H 500 h 500 mg/kg nutmeg, 14.0 (10.1-19.5); A 1000 A 

1000 mg/kg nutmeg, 23.0 (16.1-32.9). 

large dose (Figure 3). Gas-chromatographic analysis of this oil showed the 
presence of volatile components similar to groimd nutmeg, but no increased 
concentration of the myristicin, as expected from the selected distillation 
temperature.- 

- These analyses and supplies of ground nutmeg were kindly furnished by Dr. William K. Stahl, 
McCormick and Company, Baltimore, Maryland. 



218 




LOG DOSE - TRYPTAMINE, ing./kg. 

Fig. 3. — Effect of synthetic myristicin samples and oil of nutmeg concentrate on trypta- 
mine convulsive threshold in mice when given orally in acacia suspension 18 hr before 

test: X X Control, CD50 mg/kg (±95% confidence limits) 25.0 (15.2-41.0); 

O O Myristicin sample 1 at 500 mg/kg, 8.7 (5.7-13.4); O — . . • O myristicin 

sample 2 at 500 mg/kg, 14.0 (9.3-21.0); oil of nutmeg concentrate 500 

mg/kg, 20.5 (14.5-28.9); H h oil of nutmeg concentrate — 1000 mg/kg, 27.0 

(19.9-36.7). 

In Figure 4 the slope and activity of the best tryptamine assay for myois- 
bicin is compared to tranylcypromine and iproniazid. All three drugs were 
administered orally 18 hours before the test. It may be seen that myristicin 
is less potent but parallel to the comparative drugs. Saf role, isoborneol, and 
geraniol, which are other volatile components of nutmeg, did not cause po- 
tentiation of tryptamine in doses up to 1 g/kg despite obvious signs of hyper- 
activity and excitement in the mice. 

In Figure 5 the antagonism of reserpine ptosis in rats was used to study 
variations in dose and time for myristicin activity. Myristicin appears 
to be less active in the rat. Comparable activity to other MAO inhibitors was 
obtained only with the largest dose 17 hours after oral administration. 

Myristicin treatment of six rats increased brain 5 -hydroxy trptamine from 
control values averaging 0.48 (± 0.05) Mg/g to 0.82 (± 0.03) /xg/g when 
given in an oral dose of 1 g/kg; the difference was statistically significant 
(p <0.001) . Lower doses were not significantly active. 

A further test of an hypothesis of monoamine oxidase inhibition was con- 
ducted using the kynuramine disappearance rate in brain homogenates as 



219 




0.5 1.0 1.5 2.0 



Fig. 4. — Effect of monoamine oxidase inhibitors and synthetic myristicin on tryptamine 
convulsive thresholds in mice when given orally in acacia suspension 18 hr before 

test: X X Control, CDjo mg/kg (±95% confidence limits) 25.0 (15.2-41.0); 

O O 150 mg/kg iproniazid, 10.4 (8.8-12.2); A. . . .A 4 mg/kg tranyleypromine, 

5.8 (4.4^7.7); +- . . . + 500 mg/kg, 8.7 (5.7-13.4). 

described by Weissbach et al. {16) The results of this test are shown in 
Table 3. Slight inhibition was found in the mouse but not in the rat-brain 
preparation. One year after these data were obtained, the same ground- 
nutmeg source was completely inactive in the mouse as well, and the declin- 
ing activity was attributed to a loss of volatile components owing to a nearby 
heater. 

Discussion 

Although the myristicin fraction from oil of nutmeg originally used in 
these experiments might not represent 100 percent myristicin, both this and 
elemicin most likely produce similar actions. The potency of myristicin is 
not adequate in most of these tests to account for the full action of nutmeg. 
The insufficiency is present with intravenous doses and therefore poor absorp- 
tion is not a likely explanation. More rapid biodegradation of purified myris- 
ticin in contrast to its slow release from nutmeg might suggest a greater 
efficiency of the crude drug. 

These data demonstrate a mild degree of monoamine oxidase inhibition by 
a variety of tests. The low potency of myristicin in comparison to tranylcy- 
promine, a potent inhibitor, is in keeping with the large doses required for 
in vivo activity. The tryptamine potentiation test, although indirect, has been 



220 



shown to correlate with other in vivo assays. (17) It is quite likely that al- 
though myristicin displaces kynuramine from MAO with difficulty, it still 
may show inhibiting activity. 

The main virtue of these data may be to reawaken interest in myristicin 
and its activity. Low activity of a prolonged nature, such as that shown by 
nutmeg, is sometimes a more useful drug attribute than high potency and 
rapid onset. An important question remains to determine if the myristicin 
stimulation is inevitably followed by depressed feelings, even upon continued 
intake. Work is indicated to improve absorption, and further pharmacologic 
studies are needed to define a proper course of treatment for nutmeg intoxi- 
cation. 

Summary 

A myristicin-elemicin fraction of oil of nutmeg produces many of the 
characteristics of crude ground nutmeg, but lacks adequate potency to ex- 
plain the nutmeg intoxication syndrome on a quantitative basis. Nutmeg and 



90- 



80- 



o 

uj 60- 

_j 

m 

^50 
o 

Q. 

>M0H 



J2 30 

in 

o 

^ 20 



10 



0-" 



MYBISTICIN-500m) /IJ 1 P 
17 MRS PBIOB 




PARNATE -4iHa nij ,1 P 



^^B UHTREATEO IMP ^iSERPl 



4 



"7 



24 



HOURS AFTER TREATMENT 



Fig. 5. — Effect of monoamine oxidase inhibitors and various schedules of myristicin on 
reserpine ptosis in rats. Ptosis score: 0 = Eyelid fully open — 5 = Eyelid fully closed. 
Maximum score = 10/rat (both eyes). Group ptosis score (%) 
_No. rats/group X Max score/rat 



Sum of group eyelid scores 



X 100. 



221 



Table 3. — The effect of ground West Indian nutmeg on brain monoamine oxidase (MAO) 
activity in mice and rats measured by the kynuramine (Kyn) method of Weissbach, etal. 
{16) 



Species 


No. 


juM-ynK/mg/hr X lO-^o 


No. 


Nutmeg treated 










percent of control 


Mouse 


14 


3. 64± 0.013 


10 


78. 0±4. 2% 


Rat 


6 


4. 74±0. 18 


5 


104. 0±5. 5% 



" Micromoles of kynuramine/mg of brain (wet weight) /hour x 10~3. 
h 18 hours after 600 mg/kg— mice or 1000 mg/kg— rat, P.O. 



the synthetically made myristicin demonstrate a mild degree of monoamine 
oxidase inhibiting activity by in vitro and in vivo tests. Activity of this syn- 
thetic product declines with aging accompanied by color change. Monoamine 
oxidase inhibition and other actions of crude extracts depend upon the vola- 
tile component. 

BIBLIOGRAPHY 

(1) Hanzlik, p. J., "Purkinje's Pioneer Self-experiments in Psychopharmacology," 

California and Western Medicine, 44 : 1, July-August, 1938. 

(2) Waebukg, O. "Die Muskatnuss" Leipzig, 1897. 

{3) CusHNY, A. R., "Nutmeg Poisoning." Proceedings of the Royal Society of Medicine 
39: 1(3), 1908. 

(4) Tetjitt, E. B., Jr. E. Callaway, III, M. C. Braude, and J. C. Keantz Jr., Journal of 

Neuropsychiatry, 2 : 205, 1961. 

(5) Wallace, G. B., In Contributions to Medical Research, Vaughn, Ann Arbor, Mich- 

igan, 1903, pp. 351-364. 

(6) JuESS, F., "On Myristicin and Some Closely Related Substances," Berlchte, Schim- 

mel & Company, Leipzig, 1904. 

(7) Dale, H. H., Proceedings of the Royal Society of Medicine, 23 : 69, 1909. 

(8) PowEE, F. B. and A. H. Sal way, American Journal of Pharmacology, 80, 563-580, 

1908. 

(5 ) Shulgin, a. T., Nature ( Lond. ) , 197 : 379, 1968. 

(10) Casida, J. E., J. L. Engel, F. G. Esaac, F. X. Kamieuski, and Kxjwatsuda. Science, 

153 : 1130-1133, 1966. 

(11) Tedeschi, D. H., R. E. Tedeschi, E. J. Fellows, Journal Pharmacology and Ex- 

perimental Therapeutics, 126 : 223, 1959. 

(12) Litchfield, J. T., and F. Wilcoxon. ibid., 96 : 99, 1949. 

(IS) Rubin, R., M. H. Malone, M. H. Waugh, and J. C. Bukke. 120: 125, 1957. 
(H) Mead, J. A. R., and K. F. Fingee, Biochemical Pharmacology, 6 : 52, 1961. 

(15) Bogdanski, D. F., a. Pletschee, B. B. Beodie, and S. Udenfriend. Journal of Phar- 

macology and Experimental Therapeutics, 117 : 82, 1956. 

(16) Weissbach, H. V. T. E. Smith, J. W. Daly, B. Witkop, and S. Udenfeiend. Journal 

of Biological Chemistry, 235 : 1160-1163, 1950. 
(11) Maxwell, D. R., W. R., Geay, and E. M. Tayloe. British Journal of Pharmacology, 
17 : 310, 1961. 



222 



Discussion 



Chairman — Edward B. Truitt, Jr. 
Members of the Panel — Claudio Naranjo 

Thornton Sargent 
Alexander T. Shulgin 
Andrer T. Weil 

Chairman Dr. Truitt: "We might begin with a comment. One of the 
guests found that there is a whole state in our fifty in the Union that has 
a reputation for nutmeg, and perhaps he would like to make his comment 
again, which was quite interesting : that of a psychotogenic substance identi- 
fying a state. 

Dr. Phillips (from the floor) : I am a psychiatrist. I understand that 
Connecticut is known as the Nutmeg State, and I remember when I was in 
college about twenty years ago there was some reference to the fact that 
people in Connecticut acted awfully crazy, because they ate so much nutmeg. 

Mr. Weil: I am afraid the origin of Connecticut's nickname is some- 
what less romatic. In colonial times, Connecticut traders often palmed off 
carved wooden nutmegs as the real thing. This practice was considered a 
fine example of Yankee shrewness in business; consequently, Connecticut 
acquired the name "Nutmeg State". 

Chairman Dr. Truitt: I wonder if Dr. Naranjo would like to discuss 
the activity of the compound he is engaged in testing ? 

Dr. Naranjo: This amphetamine substituted with the methylenedioxy 
group is the first that was tested. The subjective reactions had been de- 
scribed by Gordon Alles from experimentation on himself. It was first used 
in a group of subjects under the assumption that this would be a hallucinogen, 
as suggested by Dr. Alles. This did not appear to be quite the case, for the 
drug produced only enhancement in feelings. In the face of this, it was sug- 
gested that it could be used as facilitating agent in psychotherapy. It is 
not something to be used as an antidepressant, but only to increase com- 
munication during a therapeutic session. 

When we used this compound on patients with psychoneurotic symptoms, 
we saw that the effects were sometimes very dramatic in an unexpected way. 
I have tried several drugs to facilitate psychotherapy, including the more 
widely known hallucinogens, and never as with this compound has there 
been such a frequency of reminiscence of childhood events, in a very dramatic 
and spontaneous way, completely unexpected by the subjects. 

This has been described in therapy with LSD and mescaline, but in my 
own experience has occurred spontaneously only once in approximately 
fifty experiences with LSD (though I understand that if a therapist searches 
for this, it could be precipitated). On the other hand, about half of the 
persons who in a therapeutic setting took this compound, (MDA), had this 
kind of experience an experience with almost no symbolic content, without 



223 



the aesthetic or mystical overtones that is so characteristic of most hallu- 
cinogens. 

This was quite rare and, in turn, there was the experience of reminiscence. 
It is notable that in many of the subjects there was amnesia after it, and 
this was very much like the similar events that take place sometimes in the 
hypnotic trance. In two instances out of thirty, at least, the effects were 
those of a delirium, and in one of these there was erratic behavior, none 
of which was remembered afterwards. 

Now with the trimethoxy substituted compound, which has been pre- 
viously described as evoking hostile reactions when we used this in a thera- 
peutic setting, this did not occur overtly ; but the compound was remarkable 
in that the delusional content was more frequent that with any of the 
others that I know. This delusional content was very often paranoid. 

Chairman Dr. Trott : Could I ask if there were any color effects, which 
are characteristic of mescaline, seen with it? 

Dr. Naranjo: This produces the greatest incidence of color effects, 
whereas the previously mentioned one, (MDA), is notable for the absence 
of distortions and color effects. 

The 3-methoxy-4,5 methylenedioxyamphetamine, (MMDA), has a meth- 
ylenedioxy bridge in common with MDA, but has the oxygen substitution 
pattern of TJMA. MMDA produces the qualities of both, and what is typical 
of this substance is that the experience, which has mostly a personal quality, 
enhancement of feeling, warmth, but very little symbolic content, makes 
it different from mescaline. 

Chairman Dr. Truitt: There is one point, I think, that many people 
have possibly underestimated, and that is the theoretical importance 
of this aspect, which is pointed out by one question from Dr. Waser : "What 
is the evidence for direct amination of the olefinic side chain of myristicin 
in the body?" 

Dr. Shttlgin : Dr. Sargent mentioned one experiment where the forma- 
tion of amphetamine in rats was actually observed. Administration of allyl- 
benzene led to chromatographically distinct spots, with the strong impli- 
cation that these spots were amphetamine. Although allylbenzene may be 
converted to propenylbenzene first, the simple addition of ammonia to the 
allyl double bond would be the most direct route. I don't know if it has 
any validity. 

Chairsian Dr. Truitt: We have a related question: "Could the 
transformation of a non-saturated aromatic side chain to a carbonyl group 
be possible?" 

Dr. Shttlgin: I don't know of this specific transformation having 
occurred. Certainly the double bond can participate in oxidation reactions, 
and substitution isomers have been converted to their corresponding acids 
in the body. Therefore the double bond is capable of being oxidized, or at 
least partially oxidized. 

Chairjian Dr. Truitt: We have two questions apparently directed to 
Mr. Weil, and I wonder if he would like to read them and comment. 



224 



Mr. Weil, : The first one is, "What are the comparative psychoactivating 
potencies of nutmeg and mace ?" 

They are the same, but mystiques about the uses of the two spices have 
sprung up. It is interesting, for example, that at Haverford College stu- 
dents believed they could only get "high" with mace, even though they knew 
nutmeg to be very similar in taste. Other groups use nutmeg only, aaid are 
unaware of mace as an intoxicant. 

The second question is, "Do other kitchen spices have any psychoactive 
properties?" 

Who knows? Perhaps in five years we will have a symposium just on 
spices. I have received scattered reports on the use of cinnamon for these 
effects : One bit of information is that cinnamon sticks are smoked by cer- 
tain Indian tribes of Mexico. I have no documentation for this report. 

People who are avid for experimenting with possibly active substances 
often try spices. In fact, a distant friend writes that anything in the spice 
cabinet except monosodium glutamate will get you "high". Ginger, paprika, 
cinnamon and pepper have all been said to have effects on the mind, but 
we have no reliable evidence on them. 

Chairman Dr. Truitt : We really must resolve the action of somatic input 
on the gastrointestinal tract, and other sources on the psychic effects before 
we accept them, too. 

I am a little chary of the next two questions. I have an antagonistic ques- 
tion from Dr. Efron, and a protagonistic question from Dr. Kline. 

Dr. Efron (from the floor) : Being a pharmacologist, I would like 
to comment on the phannacology of the tested compounds. Dr. Truitt has 
really done an excellent pharmacological job but I have some small objections. 

First, in my opinion the psychopharmacology testing is such a difficult 
one that we never can use one or two tests. One has to use a battery of tests, 
and even then, often we are not sure what they mean. 

In this case, you have put all your chips on the monoamine oxidase 
inhibition. If this would be really the only action of these drugs, then we 
should forget about them, because we have much more potent reversible and 
irreversible monoamine oxidase inhibitors that we can use. 

Further about the test that you used: the antagonism to reserpine, we 
all now agree that it is not valid as an antidepressant activity measurement. 
It was used for tricyclic types of drugs, and even then there was a. question 
as to its validity. Is there a correlation between this test and the activity of 
nutmeg ? 

The other problem I would like to comment on is that I really don't know 
why everybody is working with myristicin, the compound represented mostly 
in this large mixture of compounds found in nutmeg extracts. There might 
be a possibility that one of the other compounds present in a very small 
amount may be much more potent. 

The next thing that would be very interesting would be to elucidate for 
structural-activity relationship, and to see the activity of all the compounds 
in some battery of tests. Then we really could see how the location of one 



225 



methyl group, adding another methyl group or taking one off, affects the 
activity of the compounds. 

Chairman Dr. Truitt: Thank you very much, Dr. Efron. I fully agree 
with your comments. 

Dr. Kune: Dr. Efron's remarks are as a pharmacologist; mine are as a 
psychiatrist. 

The anti-reserpine part of the story is the one I am protagonizing for 
you. A very curious cycle is involved, because every drug which has been 
useful in the treatment of schizophrenia or the major psychoses has pro- 
duced Parkinsonism as one of its side effects. Another part of the curious 
business is that the monoamine oxidase inhibitors or other antidepressants, 
if given in large enough doses, will produce hallucinations, delusions and 
uncontrolled euphoria. 

All this woiild seem to tie somewhere into the extrapyramidal system. 
We reviewed this problem a few years ago with Mettler, and although there 
is a lot of presumptive evidence, one cannot yet dra,w a comprehensive 
picture. At a meeting which Dr. Efron chaired last year, it was pointed out 
that tricyclic antidepressants reduce the frequency of extrapyramidal side 
effects from phenothiazines and reserpine. The rats and mice who developed 
reserpine depression were given much higher doses per kilogram than we 
use on humans. When asked how one judges if depression is present in 
rats and mice, the answer was that this is judged upon the basis of reduced 
activity and reduced "sociability" ; i.e. they didn't go poking around at each 
other. Then I asked: "What about Parkinsonism in the rats and mice?" — 
and I discovered to my amazement that the animals were barely able to 
move because they were so Parkinsonized. What was called depression might 
simply be the fact that the animals couldn't get to sniff their neighbors. The 
monoamine inhibitors, and perhaps the tricycle antidepressants, act as anti- 
parkinsonian agents. Professor Holmstedt mentioned yesterday that Lewin 
has found harmine, a monoamine oxidase inhibitor, useful in the treatment 
of Parkinsonism. 

Chairman Dr. Truitt : I heartily agree with you. Dr. Kline, because you 
recognize our problems in the laboratory. We have a great deal of difficulty 
in defining these parameters, isolating them, and analyzing them. Cer- 
tainly I would be the first to disclaim that we can extrapolate easily 
this way from a test to the whole animal. When we speak of the 
appearance of tremor and absence of tremor or antagonism of tremor, we 
are dealing with a fairly precise parameter. Wlien we are speaking of emo- 
tional effects rising and falling, we are speaking of a complex set of behavior 
changes that we ha,ve a healthy respect for. 

A couple of other related questions that might follow Dr. Kline's. This 
is from Dr. Buckley: "Does myristicin have anticholinergic activity?" 

Only in the respect that generally anticholinergic activity in the CNS is 
in some ways similar to potentiation of adrenergic activity. We have not 
specifically tested this in any respect. 

"Does myristicin inhibit adrenergic reuptake of norepinephrine by the 
nerve endings?" 



226 



This is postulated as the mechanism of action for the tricyclic antidepres- 
sants. This hypothesis is too new for our consideration. If it is, perhaps a 
combination of a weak monoamine oxidase inhibitor, such as nutmeg, and 
the trycyclic agents, might be of interest. 

Going to the more physical aspects, we have a question from Dr. Beavers, 
concerning the effects of nutmeg on blood pressure in human subjects, and 
asking whether we have any evidence of monoamine oxidase inhibitors either 
increasing or decreasing effects of nutmeg in humans. We certainly need to 
know more about this. Dr. Naranjo, have you done blood pressure examina- 
tions with the compound ? 

Dk. Naranjo: There is slight variation in blood pressure. There is occa- 
sionally an increase but this is not consistent, and it is hard to evaluate 
to what extent the observed changes are secondary to the emotional states, 
for sometimes anxiety is a prominent component of the induced reaction. 

No lowering of blood pressure has been observed. This is in contradiction to 
the observations on some persons who experienced intoxication with nutmeg. 

Chairman Dr. Trupit : Dr. Leake has a question. 

Dr. Leake: I want to amplify a point made by Dr. Efron. This con- 
cerns the systematic investigation of all of the phenyl amines. This actually 
was Dr. Gordon Alles' undertaking, as you know. One extremely important 
feature of it I would recommend to all workers in the field. It bears on some 
of the reports that were made today. Even though chemical compounds in a 
series are very close, insofar as their molecular weights are concerned, Gordon 
Alles insisted on using equal molecular concentrations so as to compare each 
drug with the other on a molecular basis. This is important, particular when 
there is any significant difference in molecular weight. 

Alles had an enormous amount of material that has never been published, 
and I don't know whether it will be. He made a methylenedioxy derivative 
of an amphetamine, in which he found extraordinary enhancement of audi- 
tory sensation. This he did describe informally at one of the Macy Confer- 
ences. This compound produced another remarkable effect: if he were to 
strike his finger, he could see the strike, and feel it afterwards by a definitive 
period of time. 

Dr. Shtjlgin : That was the methylenedioxyamphetamine compound that 
we called MDA earlier. 

Dr. Leake : He made similar observations of this sort on other com- 
pounds. Since he had them all on an equal molecular basis, and since he did 
most of the experimentation on himself as one subject, at least his findings 
had that comparative validity. 

Dr. Marrazzi (from the floor) : In line with what is being said, and 
the comparison with mescaline, I thought you might be interested in the 
comparison that we have been making of methoxyphenylethyl amines, using 
cortical synaptic inhibition. At the moment it looks like mescaline (a tri- 
methoxy compound), would have a potency of 1, the dimethoxyphenylethyl- 
amine of 1.8, while the demethylated or dihydroxyphenylethylamine, dopa- 
mine, would have a potency of 10. 



227 



This is reminiscent of the old work of Gunn, which showed that the meth- 
oxylation has a muzzeling action, decreasing activity. Apparently in pre- 
liminary data it seems to decrease cortical inhibitory activity. 

Chairman Dr. Trtjitt : How much do you think this variation in activity 
is due to rate of transfer across the blood-brain-barrier, and how much to the 
differences in actual potency ? 

Dr. Marrazzi: I am not able to answer that. These are closearterial 
injections, and the latency of beginning action is approximately the same. 
It should be measured more carefully than I have done so far, but there is 
no remarkable difference, which would suggest that it is not a difference in 
passing through the blood-brain-barrier. 

Chairman Dr. Trtjitt : We have a question directed to Dr. Shulgin and 
Dr. Sargent: "Could you describe your human bioassay methods further?" 

Dr. Shulgin : The human bioassay follows a preliminary pharma- 
cological and pharmacodynamic analysis of the investigated material on 
animals. Generally, three species, the mouse, the rat and the dog, are used. 
Most of the cardiovascular work is done on the dog. The compounds were 
then assayed within our experimental group. The human threshhold level 
was established by successively increasing the dose in small increments until 
this level was reached. This testing and the subsequent psychopharma- 
cologic comparisons of the several compounds were done essentially by the 
"double conscious" method of Alles. (see our reference 10) . 

Dr. Sargent: I would like to comment on the remarks of Dr. Efron 
and Dr. Leake, as far as the structure-activity relationship studies go. 

Actually this was originally Dr. Shulgin's and my interest in investigating 
these compounds, and we could perhaps elaborate a little bit on one of the 
slides in which two other substituted phenylisopropylamines are mentioned, 
the precursors of which are not present in nutmeg. They were tested speci- 
fically to measure the effect of the orientation of these methoxy groups. 

Our scale in mescaline units is the same as Dr. Leake's. However, we assign 
some of the numbers a little differently from his. We grade LSD as 3000 in 
mescaline units, the effect dose being a tenth of a milligram. 

Dr. Leake : You understand that my grading was off the cuff. 

Dr. Sargent: I might mention in regard to the previous discussion 
of Parkinson effects of harmine and harmaline, these compounds are also 
hallucinogenic. To get back to the structure- activity relationships of these 
methoxy-substituted amphetamines, which are summarized in our figure 7, 
note that when the structure of TMA with the 3,4,5-methoxy substitutions is 
changed to 2,4,5-, or TMA-2, the activity in humans of the compounds is in- 
creased tenfold. Again, when the structure of the 3-methoxy-4,5-methylene- 
dioxy compound, MMDA, is changed to 2-methoxy-3,4-methylenedioxy or 
MMDA-3a, the activity is again increased, this time by a factor of 6. In both 
cases, the change of a methoxy group from a meta- to an ortho-position 
markedly increased the potency of the compound. The more active compounds 
are derived from croweacin and asarone, which occur in natural oils but not 
oil of nutmeg. 



228 



Chairman Dr. Truitt: We have one last question that I would like to 
direct to Mr. Weil: "What significance would you give to hypothermia 
observed after nutmeg intake ? " 

Mr. Weil: In the acute intoxications that have come to clinical atten- 
tion — and there have been few — a number of symptoms suggestive of vasomo- 
tor instability has been noted. I suspect that many of the constituents of nut- 
meg might have effects on the autonomic nervous system and on general 
homeostasis that we have not spelled out very well: possibly, this fall in 
temperature is one of them. 

Chairman Dr. Truitt: This is the end of our time for this afternoon. 
I thank you again for your indulgence. 



229 



SESSION IV 



SOUTH AMERICAN SNUFFS 

Bo Holmstedt, Chairman 



Anthropological Survey of the Use 
of South American Snuffs 



S, Henry Wassen 

Gothenburg Ethnographic Museum, Gothenburg, Sweden 

Page 

Early Reports and Archeological Evidence from the West Indies and the Continent 23S 



Introductory Remarks 233 

The Cohoba Sniifts and Its Paraphernalia 234 

Further Details About the Cohoba Powder 237 

Archeological Evidence for the Use of Snuff 243 

Ethnographical Data About the Use of Snuffs in South America 262 

Comparative Outlooks and Symbolism 274 

Bibliography 286 



Early Reports and Archeological Evidence from the 
West Indies and the Contents 

Introductory Remarks 

The first contacts between Amerindians and Columbus and his men were 
established in the West Indies. It is also from the Antilles and the surround- 
ing mainland that we have our first information about the Indians' use of 
what we now understand to have been a psychotomimetic snuff. Although 
this early information is limited, and not until our days has it been really 
considered to its full worth, it is of outstanding importance. Thus, at least 
some evidence has been saved in the reports of the chroniclers from the 
Circum-Caribbean culture area, for, as stated about the tribes referred to 
as Circum-Caribbean, "whether insular or on the mainland, they were readily 
accessible from the coast, and were quickly overrun by the Spanish con- 
querors. The great majority of them have long been extinct culturally if not 
racially." ^ 

The difficulty in defining what plant material an early description refers 
to must be considered in any serious study. In my opinion we cannot, as 
Jerome E. Brooks has done in his work on tobacco ( 1937) ,^ take it for granted 
that observations by Amerigo Vespucci during his voyage with Alonso de 
Ojeda and Juan de la Cosa (May, 1499-June, 1500), bear on tobacco chew- 
ing- — even though many kinds of American tobacco later have been observed. 
These observations related, supposedly, at least, to natives of Margarita 
Island, off the coast of Venezuela. 

According to Brooks (1937 : 189), Vespucci's notice in his letter of 1504 
to his friend, Piero Soderini, "was the first published which relates to a 

1 steward, Julian H. 1948 : 1. 

2 Brooks, Jerome E. 1937 : 189. 

233 

262-016 O — 67 ^17 



habit we know to have been tobacco chewing." I quote the following from 
Vespucci's description in the rendering presented by Brooks : 

The customs and manners of this tribe are of this sort : In looks and behavior they 
were very repulsive, and each had his cheeks bulging with a certain green herb which 
they chewed like cattle, so that they could scarcely speak, and each carried hanging 
from his neck two dried gourds, one of which was full of the very herb he kept in his 
mouth ; the other full of a certain white flour like powdered chalk. Frequently each put 
a certain small stick (which had been moistened and chewed in his mouth) into the 
gourd filled with flour. Each then drew it forth and put it in both sides of his cheeks, 
thus mixing the flour with the herb which their mouths contained. This they did very 
frequently a little at a time. 

From the continuation of the description, we deduct that the European ob- 
servers believed that the natives "carried the herb and flour in their mouths 
in order to relieve their thirst", and, also, "that the women did not them- 
selves indulge in the habit" (Brooks 1937: 191). 

If we now should give a description of how e.g. the actual Kogi (or Ka- 
gabba) Indians of Sierra Nevada de Santa Marta in Colombia use their 'po- 
foro (bottle-shaped gourd for lime) and chew their coca {hayo)^ a process 
that I myself have observed many times, we could word for word repeat the 
description quoted from Vespucci. As a matter of fact his words can as 
well refer to the habit of coca chewing. Such an eminent Americanist as Er- 
land Nordenskiold of Gothenburg considered Vespucci's words as clearly 
referring to coca,^ and Cooper (1949: 549) has included the Cumana area 
of Venezuela among the regions from which "early historical sources report 
coca chewing and/or ritual use of coca leaves as prevalent." To this must be 
added also the observation by Vespucci that "the women did not themselves 
indulge in the habit." No rule is without an exception, but just as an addition, 
I wish to add that "more commonly, coca chewing is a masculine rather than 
a feminine habit" (Cooper 1949: 552). 

The Cohoba Snujf and Its Paraphernalia 

The cohoba snuff used by the Taino of the West Indies has, as we know, 
caused much discussion which I previously tried to summarize in two papers.* 
"We must note that Columbus himself observed the use of a powder, though 
he does not mention it by name. During his second voyage, 1493-1496, 
Columbus not only commissioned the Friar Ramon Pane to undertake what 
we now call anthropological field work among the aboriginal population 
of Espanola ("to collect all their ceremonies and antiquities," Bourne 
1906: 4), but he himself made valuable observations presented in his nar- 
rative of the second voyage.^ As has been pointed out by Bourne, we possess 
this narrative "only in the abridgment of Las Casas and Ferdinand Colum- 
bus." The original is lost,'' but both Las Casas and Ferdinand Columbus "in 

3 Nordenskiold, Erland, 1919 : 14. 

* Wass4n, S. Henry and Bo Holmstedt. 1963 : 27-35 ; Wass6n, S. Henry. 1964 : 97-120. 
Bourne, Edward Gaylord. 1906 : 3, quite correctly has credited Christopher Columbus as the 
person who "set on foot the first systematic study of American primitive custom, religion and 
folklore ever undertaken." 

» Bourne. 1906 : 4, "The original Spanish text of these documents Is no longer extant and, like 
the Historie which contains them, they are known in full only in the Italian translation of that 
work published In Venice in 1571 by Alfonso UUoa." 



234 



condensing the original, incorporated passages in the exact words of the 
Admiral. It is from such a passage in Ferdinand's abridgment that we derive 
the Admiral's account of the religion in primitive Hayti" (Bourne 1906 : 4) . 
Ferdinand Columbus says that he recorded "the very words of the Admiral", 
and we can now, in Bourne's translation (p. 4-6), find the following in- 
formation of a powder which evidently must be the same as that mentioned 
by Ramon Pane as cohoba: 

I was able to discover neither idolatry nor any other sect among them, although all 
their kings, who are many, not only in Espanola but also in all the other islands and 
on the mainland,' each have a house apart from the village, in vi^hich there is nothing 
except some wooden images carved in relief which are called cemis ; * nor is there 
anything done in such a houae for any other object or service except for these cemis, by 
means of a kind of ceremony and prayer which they go to make in it as we go to 
churches. In this house they have a finely wrought table, round like a wooden dish in 
which is some powder which is placed by them on the heads of these cemis in perform- 
ing a certain ceremony ; then with a cane that has two branches which they place in 
their nostrils, they snuft up this dust. The words that they say none of our people 
understand. With this powder they lose consciousness and become like drunken men. 

In addition to the secluded cemi houses for snuffing ceremonies, Columbus 
mentions two paraphernalia, namely a "finely wrought table" for the powder, 
and a "cane that has two branches" to snuff up this dust. Both are of im- 
mediate interest. 

In a paper from 1964 dealing with the Neo-Indian epoch, Irving Rouse 
has referred to the statement that the Arawak in the West Indies placed 
the powder on top of cemis, adding that "many of the statues found in 
caves have a platform on top for this purpose." ^ In this connection Rouse 
has republished the 66 cm. high wooden British Museum cemi, in the shape 
of a bird standing on what seems to be a turtle. This figure, originally pub- 
lished by Joyce,^" was republished also by Wassen 1965 : fig. 4. A kneeling 
stone figure from Puerto Rico, published by Palmatary,^^ may also be taken 
into account as such a West Indian cemi with platform on top. I have in 
my work from 1966 (pp. 30-31, figs. 5 and 53) , pointed out that we still find 
a South American ethnographic parallel to this in the ceremonially used 
tabletops for snuff, and snuffing paraphernalia used among the tribes of the 
rivers Branco and Colorado in western Brazil. These tabletops are carefully 
made and polished, but according to Franz Caspar's observations among 
the Tupari, the table has no special function beyond its mechanical use 
during the snuffing seances.^^ We can observe that the snuffing ceremony 
among the Tupari takes place inside the house. When used, the tabletop 
is supported by three wooden legs on which it is loosely placed. The table- 
tops are irregularly square-shaped and provided with a handle. They are 

'' According to Bourne, Cuba, which Columbus believed to be the mainland. 

* Bourne. 1906 : 5, footnote. "Ulloa in his Italian gives this word in various forms e.g. cemij 
cimi, cimini and cimiche. The correct form is cemi, with the accent on the last syllable. Las Casas 
says, "Estas — Uamaban cemi^ la ultima silaba luenga y aguda." 

» Rouse, Irving. 1964 : 510-511. 

"Joyce, Thomas A. 1916, pi. 21. 

" Palmatary, Helen C. 1960, pi. 120 d, and text on p. 92. 

" The photo published in Wassen, 1965, fig. 5, was taken by Dr. Franz Caspar among the Tupari, 
during his second expedition to this tribe in 1955. 

235 



Fig. 1. — Y-shaped snufEng tube from Haiti. After Oviedo. 




cut from the wood of flat supporting roots of a tree. Dr. Franz Caspar con- 
siders them as particular for the tribes of the Branco and Colorado Rivers. 

If we now turn to the "cane that has two branches", Columbus evidently 
was observing the use of Y-shaped snulRng tubes, of which there were finely 
worked ones used by the chiefs and principal men, and others made of 
reeds for those who could not afford the finer ones. The "poor hermit" 
Ramon Pane apparently does not refer to a forked tube when he says that 
"the Gogioha is a certain powder which they take sometimes to purge 
themselves, and for other effects which you will hear of later. They take 
it with a cane about a foot long and put one end in the nose and the other 
in the powder, and in this manner they draw it into themselves through 
the nose and this purges them thoroughly" (Bourne 1906: 17; cf. Loven 
1935: 393). 

In Wassen 1964 (pp. 102-103), there is a discussion of the West Indian 
snuffing instruments according to the sources, and I here again republish 
the tube from Haiti (Fig. 1) which we find in the work by Oviedo," who 
also has stated that it was the Y-shaped snuffing instrument, and not the 
plant, which was called tabaco by the Indians (vol. I: 131). The famous 
Bishop and Historian, Bartolome de las Casas, also described the West In- 
dian snuffers, "made in the size of a small flute, all hollow as is a flute." To 
make his readers understand the Y-shaped form of the instrmnent, he uses 
the picture of the fingers in an out-stretched hand.^* 

Even if we accept the occurrence in the West Indies of Y-shaped snuffing 
tubes as an obvious parallel to tubes of the same type found in South America, 

The original is found in volume I, pi. 1 : 7, of Oviedo's Historia general, etc. (1851). The 
corresponding text on p. 130. 

Las Casas, Bartolom6 de. 190!> : 445. ". . . ; la liechura de aquel instrumento era del tamafio 
de una pequeiia flauta, de los tercios de la cual en adelante se abria per dos cafiutos huecos, de la 
inanera que abrimos los dos dedos del medio, sacado el pulgar, cuando extendemos la mano." 

236 



we must also note the observation made by Loven (1935:393), that "the 
Tainos differ from the whole South America in that their forked snuff- 
tubes were not made from bones, and certainly not from those of birds, as 
in the Orinoco and Cayary-Uaupes regions. Suitable bones for tubes were 
not accessible on Espanola ; other material had to be sought there." 

We find another parallel between Haiti and the northern South American 
mainland, in the round trays for snuff now found among the Indians of the 
Orinoco region (see Wassen 1965, fig. 1, p. 21), and the fine and polished 
round trays described by Las Casas from the island. He says that the snuffing 
instrument was made of the same kind of dark wood as the tray.^^ 

That the snuffing tubes of wood used on Haiti in some cases were fine 
pieces of sculpture is clearly understood from the specimen found at La 
Gonave (Fig. 2), first published in 1941 by Mangones and Maximilien, later 
also by Rouse and Wassen." Dr. Grete Mostny of Santiago, Chile, has in a 
paper from 1958 ^® compared the elaborate tube from Haiti with specimens 
of finely sculptured straight snuffing tubes from the Atacaman region, where 
the Y-shaped tubes do not seem to exist. As the description of the tube from 
Haiti is very poor in the work by the two Haitian authors, it is fortunate 
that Mostny has been able to quote a letter from Louis Maximilien (Febr. 
11, 1956). In this, some particulars are given regarding the motif on the 
specimen found in the Picmi cave on the island of Gonave, namely a kneeling 
man crowned by a bird's head. 

Further Details about the Cohoha Powder 

At the end of his report from the second voyage, Christopher Columbus 
refers to an account he had ordered from "one Friar Roman (Ramon) who 
knew their language" (Bourne 1906: 6). As far as we know, through the 
Admiral's son and other chroniclers, who know Pane's text, "to this day our 
most authentic record of the religion and folk-lore of the long since extinct 
Tainos, the aboriginal inhabitants of Hayti" (Bourne 1906: 4), we meet 
in it not only the name of a certain powder they inhaled, but also most in- 
teresting field observations on the psychotomimetic effects of the drug. 

Friar Ramon Pane whose text is best read in the careful edition of 
Bourne,^® uses two words, cohoha and cogiolja, for a snuff used for special 

'5 For various types of South American snuffing tubes see Wassen, 1965. 

^8 In tlie text of Las Casas, 1909 : 445, a snuff tray is described as follows : ". . . plato redondo, no 
llano, sino un poco algo combado 6 hondo, hecho de madera, tan hermoso, liso y lindo, que no fuera 
muy mds hermoso de oro 6 de plata ; era cuasi negro y lucio como de azabache." 

"Rouse. 1964, fig. 18; Wassen. 1964, fig. 2, and 1965, fig. 51. The original in Mangones and 
Maximilien, 1941, pi. 50. 

18 Mostny, G. 1958 : 387-389. I quote from the text of the letter (p. 383) : "Les deux branches 
sup§rieures du Calumet se terminaient par des bouts olivaires — afin de rendre aux marines un 
contact doux — ; le point de jonction des trois branches porte le motif sculpts, reprSsentant un 
homme agenouillS, les bras liSs derrifere le dos et la poitrine incline dans une attitude de priere ; 
le tout surmontS d'une tete d'oiseau d'un haute relief." 

1" Bourne. 1906 : 8-9. "To facilitate a study of this material in its earliest record I have trans- 
lated Ramon's treatise from the Italian, excerpted and collated vyith it the epitomes of Peter 
Martyr and Las Casas, and have prepared brief notes, the whole to form so far as may be a critical 
working text of this source for the folklorist and student of Comparative Religion in America. 
The proper names in each case are given as in the 1571 edition of the Historie." — "At best the 
spelling of these names offers much perplexity. Ramon wrote down in Spanish the sounds he heard, 
Ferdinand, unfamiliar with the sounds, copied the names and then still later Ulloa, equally un- 
familiar with the originals, copied them into his Italian. In such a process there was inevitably 



237 



purposes. We have already referred to the text where it is said that "the 
Gogioba is a certain powder which they take sometimes to purge themselves," 
etc. (Bourne 1906: 17). Later, in this text, we meet the word coJioha: 

When one is ill they bring the Buhuitihu (Bohuti) to him as a physician. The physi- 
cian is obliged to abstain from food like the sick man himself, to play the part of sick 
man which is done in this way which you now will hear. He must needs purge himself 
like the sick man, and to purge himself he takes a certain ixnvder called cohoia snuffing 
it up his nose, which intoxicates them so that they do not know what they do, and in 
this condition they speak many things incoherently, in which they say they are talking 
with the cemis, and that by them they are informed how the sickness came upon him. 

Further on (Bourne 1906 : 24), a description of great interest to the psy- 
chotomimetic studies follows, which I quote: 

And when they want to know if they will 'be victorious over their enemies they go 
into a cabin into which no one else goes except the principal men ; and their chief is the 
first who begins to make cogioba, and to make a noise ; and while he is making cogioba, no 
one of them who is in the company says anything till the chief has finished ; but when 
he has finished his prayer, he stands a while with his head turned (down) and his 
arms on his knees; then he lifts his head up and looks towards the sky and speaks. 
Then they all answer him with a loud voice, and when they have all spoken giving 
thanks, he tells the vision that he has seen, intoxicated with the cogioba which he has 
inhaled through his nose, which goes up to his head. And he says that he has talked 
with the cemi and that they are to have a victory ; or that his enemies will fly ; or that 
there shall be a great loss of life, or wars or famine, or some other such things which 
occur to him who is intoxicated to say. Consider what a state their brains are in, 
because they say the cabins seem to them to be turned upside down and that men 
are walking with their feet in the air. 

I have had in my hands photographic copies of some pages of ^^P.Martyris 
Angli-mediolanensis opera Legatio habylonica Occeani decas Poemata 
Efigranvmata^'' the Gothic edition from Seville 1511, of Peter Martyr's First 
Decode. It is in this text (see Fig. 3, a-b), that the author, who never him- 
self went to the New World, after having seen Pane's manuscript deals 
with the cohoha powder. For a translation I follow MacNutt,^" however 
with some corrections and notes.^^ 

Translation of the Latin text of 1511 (fvi r. and v) : 

It is the augurs, called bovites, who encourage these superstitions. These men, who 
are persistent liars, act as doctors for the ignorant people, which gives them a great 
prestige, for it is believed that the zemes converse with them and reveal the future to 
them. 

If a sick man recovers the bovites persuade him that he owes his restoration to the 
intervention of the zemes. 



some confusion of u and n and u and v, (Spanish b). In the Italian text v is never used, it is 
always u. In not a few cases the Latin of Peter Martyr and the Spanish of Las Casas give us forms 
much nearer those used by Ramon than the Italian." It is now clear that both Las Casas and 
Peter Martyr underestimated the Importance of Ramon Pane's worlt. For this see e.g. Bourne, p. 7. 

""MacNutt, Francis Augustus. 1912. Vol. I: 172-174. As pointed out by Wass4n, 1964: 105, 
Ramon Pane used buhuitihu and bohuti. This evidently Island-Arawak word has been latinized into 
boitius (pi. boviti) by Pedro Martyr and is written buhuti by Ovledo, and bohique and behigue by 
Las Casas. If we try to connect it with other known words, we are probably safe to do so with the 
also Island-Arawak buMo, boMo, a common word in the Spanish reports for house but sometimes a 
designation for special houses, very probably also those for medicine-men's cures. 

^ The first printing of Decade One which was authorized by Martyr is that of 1516, in which 
the plural boitii for medicine-men occurs. 



238 




Fig. 2. — Sculptured snuffing tube of wood from La Gonive, Haiti. L. 24 cm. Taino 
Culture. After photographs published by Mangones and Maximilien. 

When they undertake to cure a chief, the bovites begin by fasting and taking a purge. 
There is an intoxicating herb which they pound up and drink," after which they are 
seized with fury like the maenads, and declare that the zemes confide secrets to them. 
They visit the sick man, carrying in their mouth a bone, a little stone, a stick, or a 
piece of meat. After expelling every one save two or three persons designated by the 
sick person^ the bovite begins by making wild gestures and passing his hands over 

23 MacNutt translates drink. The Latin text has sorheo, absorb. 
23 The Latin says : "from a semicircle," etc. 



239 



mcdiolanenlie oper$^ 

Fig. 3 a-b. — Title and text, fvi(r.), in Peter Martyr's work from Seville, 1511, in which 
Ramon Pane's notices of cohoba snufRng first appeared. After a copy in "Arents To- 
bacco Collection," The New York Public Library. 

the face, lips, and nose, and breathing on the forehead, temples, and neck, and drawing 
in the sick man's breach. Thus he pretends to seek the fever in the veins of the sufferer. 
Afterwards he rubs the shoulders, the hips, and the legs, and opens the hands ; if 
the hands are clenched he pulls them wide open, exposing the palm, shaking them 
vigorously, after which he affirms that he has driven off the sickness and that the 
Ijatient is out of danger. Finally he removes the piece of meat he was carrying in his 
mouth like a juggler, and begins to cry, "This is what you have eaten in excess of 
your wants ; now you will get well because I have relieved you of that which you ate." 

If the doctor percieves that the patient gets worse, he ascribes this to the zemes, 
who, he declares, are angry because they have not had a house constructed for them, 
or have not been treated with proper respect, or have not received their share of 
the products of the field. Should the sick man die, his relatives indulge in magical 
incantations to make him declare whether he is the victim of fate or the careless- 
ness of the doctor, who failed to fast properly or gave the wrong remedy. If the man died 
through the fault of the doctor, the relatives take vengeance on the latter. Whenever 
the women succeed in obtaining the piece of meat (erroneous transl.y* which the 
bovites hold in their mouths, they wrap it with great respect in cloths and carefully 
preserve it, esteeming it to be a talisman of great efficacy in time of childbirth, and 
honouring it as though it were a zeme. 

The islanders pay homage to numerous zemes, each person having his own. Some are 
of wood, because it is amongst the trees and in the darkness of night they have received 
the message of the gods."' Others, who have heard the voice amongst the rocks, make 
their zemes of stone ; while others, who heard the revelation while they were cultivating 
their ages — that kind of cereal I have already mentioned, — make theirs of root.'" 

Perhaps they think that these last watch over their breadmaking. It was thus that the 
ancients believed that the dryads, hamadryads, satyrs, pans, nereids, watched over 
the fountains, forests, and seas, attributing to each force in nature a presiding divinity. 



^ This passage has evidently been wrongly translated by MacNutt. The women could hardly keep 
the pieces of meat. From the Latin, "de lapillis aut ossibus quos ore gestasse bouijtus aliqiiis 
putatur: se Jemine," etc., it is clear that the women collected the stones and the pieces of bones for 
the said purpose. 

^ In the original visionibus, "visions", are mentioned. 

^ "That kind of cereal" for genus panis has in the Argentine edition of 1944 been translated as 
"clase de alimento." In the Latin text of 1516 it says genus eduUi. 



240 



fieri putc9:quibccilU0redtare cwCNcmt£liiintodnCK:fiws|pO0 iaie metu ta out 
per Diucrfa fuilfe vagat06:x>cfereiam fame periitnnquia nolbibi fillat peocm aa 
oebannl^incquonia acmi8\>2gQtnciinaD|Nnro;t0Domum puirarecepcrunrca3a# 
bi.i.panan pocntes pinfo] auton in phmo igreDiaitan cofpuilFc ita acritcr fotun 
vcilUertcmrpunero?mmnrnirgioiinmt}miit(era]8:quofa^i^ 
confibo acccpto laptDcaairo apotumeffcer cuius vlcere natam aiuntfbtuna5:qua 
nuituo polKratresilUomnca vlifunnatc^ab ea feruntfiUosftUarq^gcnuinc. ju^ 
amoiu6aUuoaDucrtirop}incq>0iUu(faimiTic 2lntru5qtacaliuDiouanaboina no 
minein cuiufoamreguU oiocdi:qui i)^ac^^ec|pvocatur.3D rebgiofuie q^co^in 
tt^mquonDamautc^rTt>ammramc^ gredcolunt:acvaierannir:millevah)d ox 
natum picnuie^n t>uiu0antn foiibusouoe |;>abentrculpt093ane8:quo?um vna 
bintatteUenU]^aro|p>um alteram vocant/Corcama fpeoim coleraitpietate :infe 
iTOgati:quiarolinDelunac0lumeo}bi p:ebioiri p?ooienint:grauiter Ktifyteq^nf^ 
ponDent./ConajrrationibU0antra vduti noe v>2bcm t baticanom no(lre rdigiois 
capnt:auciCompo(leUam ^3t>aiiralem Domini fqMilcrani frequoitant. Subia# 
cent a alteri fupoilidonum gaicri:mo;nio6 pucant noctu vagari:ac vefd guanua# 
ba(fh)cmnobi6incognito)oxonoltmiU:leairq3inta'viuo8\>a:^ 
peitmubere8:rumptanamc^vinlifo2macoirex>dtevioentttna(lquomaoopu0^ 
uenimroianefcunt. Siquisauton apuofciacot moituumaliquanooruTpicatur 
(quomquiD noui fenferitin lecto) vteri attraxationereoabiofolui balbuliir. /Cun# 
aanaq^aiuntmo:tuo0po(rc|;Miinananianb2arulaperep^ fi vmbi 

licoigimrmo^niumefTeDianordctacmdiUicorer^^ iri^ 
neribud p:edpue vi)Tc0 puolide) momioeooainm viuiscrebuntnncontra quos 
fi viato; intrepiDue1laoinDiroluiffaniarma:nveropeitimdcan^ aoo?im 
C)operterrenvcr€piu6eafb}nuDinemDUioebiUtaiiuracftupeae. JnioTogahano 
fbleinfularee vnoeribicodritu6inane8tan$contagionan comparauerinna ma# 
ionbus Ipereoirariod rcTponDencrirlpmirc^ aiiit vltra (^ninu memonanuifta c6# 
fqtaqucncminem licctp:crcrr^lo}umHlio8eoocai:memoheilla comenoanr ne 
q^enimlicterae vn(^^abuercoiebufcBf€(li8(alio pulfancepopulo ) canentes vehi 
ti rolonniaracrap:eponunpin(lramenmm|?abentvmaimligneum:a}^ 
boanetanninv^cocunmrimpani^moK. l^illoeimbuunrfupcrftidonibueeo]!^ 
0Ugura0quo8boni)ta8\?ocannrantai|cmmeDtdqnip(cbecutermim infae mi# 
IUaltrauncfrauoeo.iCttDerecoguntpUban aoguitscquiafunt apoo earn au^ 
ctoHt9ti0enmie)$5eme8ipro0aUoquannrfu(arac^pxDice^ aoueifaUi 
bo»n0valitu{Hneconualuaic:reoono 5am8tDaireainimpcrruaDenr.3kiunio^ 
pQiigationireobUgantboui)K: q^aira50epnmar^ fumi^caUquo. l^crbamcK 
inmumineb:iatequ2quompuluatamro?p(mt(vdutimoiaDe8)m 
nmUa&a5emibU8anbureihumnunmt.^alimo(nariumaoeum^^ 
O0romptoautfhi(tailocarai8.Cir|;)cnucido drdnncomneapxtierpnumautouod 
quoeipraiutdegmrXiraiicp2imanum booii'titdtcrautquacer : fadem:labiana 
raq$Qtox|nen8feDi0gdlibu8:in frontsmHn tanpo:ann collum fuflar ernxxf ab^ 
rosboiaaatm : poft (^femoxbum q: labo»nfi8 venie Q:|;>aunreokit. ||^(;>u# 
tncro0Odnoeacftmo2a a ouraegrocumfncanfficdneraaa peoiboe manns ceoa 
dfattj^ncmanibue complcpeuio |?o(ttum psocmric apertum: oc inanoo cfcatit 



241 



The islanders of Hispaniola even believe that the zemes respond to their wishes when 
they invoke them. When the cacique wish to consult the zemes, concerning the result 
of a war, about the harvest, or their health, they enter the houses sacred to them and 
there absorb the intoxicating herb called koho'h'ba, which is the same as that used by 
the bovites to excite their frenzy.^ Almost immediately, they believe they see the room 
turn upside down, and men walking with their heads downwards. 

This kohobba powder is so strong that those who take it lose consciousness ; when 
the stupefying actions of the powder begins to wane, the arms and hands become loose 
and the head droops.^ After remaining for some time in this attitude, the cacique 
raises his head, as though he were awakening from sleep, and, lifting his eyes to the 
heavens, begins to stammer some incoherent words. His chief attendants gather round 
him (for none of the common i)eople are admitted to these mysteries), raising their 
voices in thanksgiving that he has so quickly left the zemes and returned to them. 
They ask him what he has seen, and the cacique declares that he was in conversation 
with the zemes during the whole time, and as though he were still in a prophetic delirium, 
he prophesies victory or defeat, if a war is to be undertaken, or whether the crops will 
be abundant, or the coming disaster, or the enjoyment of health, in a word, whatever 
first occurs to him. 

Bourne (1906: 20) accepted cohoba as a word for tobacco, and I have 
previously (see Wassen, 1964: 102) been inclined to accept the explanation 
by Friederici that the Taino word cohoha probably stood for tobacco, 
while the word cogioha should stand for Piptadenia. Brooks (1937: 189), 
however, has made it perfectly clear that "none of the early commenta- 
tors on the custom says that the substance inhaled was derived from the 
tobacco plant," and when taking into account all the forms of the word 
oohoha, such as cohohha^ cahoha^ cojoia-cogioha, cojioha, oohiba, coiba,^° I 
am now of the opinion that it is one and the same word, and that cohoba as 
Brooks (1937 : 196) expresses it "was employed by the medicine-men chiefly 
to induce a state of trance." We have every reason to believe that the cohoba 
identification by E. W. Safford and other writers as a snuff prepared from 
the seeds of Piptadenia peregrina is valid.^^ According to Brooks (1937 : 197) 
"this plant, indigenous to certain parts of South America and to some places 
in the Antilles (including Haiti), still bears the name cohoba." Here it is 
interesting to add that Pittier (1926: 189) has found the word cojoba for 
the tree used in northern Venezuela (cf. Rosenblat, 1965: 272, 344). 

In this connection I wish once again to underline the statement of Dr. Siri 
von Eeis Altschul in her botanical thesis of 1964 (p. 42) that the Indians of 
the West Indies "may have found it easier to plant the trees than to maintain 
communication with the mainland for their source of supply" (of cohoba). 
It is interesting to add that Oviedo says that the snuff came from an herb 
(hierva), which the Indians valued much, and kept it cultivated.^^ Las 
Casas mentions that the Indians "had certain powders of certain herbs well 
dried and finely ground and of the color of cinnamon or powdered henna, 

^ The Latin text has it, and this is important, that the chohobha was absorbed per nares. 
25 In the Latin edition of 1516 there is a small change in the text, ". . . insania Irachiis demisao 
capite genua complectitur . . ." 
29 Friederici, Georg. 1925. 
=" Friederici, Georg. 1947 : 198. 

=1 Already in 1898, Max Uhle (p. 9) draws the conclusion that "the extreme strength of the 
powder as described by Petrus Martyr, exceeding that of tobacco, decides its different nature and Its 
Piptadenia character." 

^ Oviedo, Hiatoria, etc. 1851 : 131. 



242 



Fig. 4. — Archaeological bird-shaped pottery snuffers from Costa Rica. A, Guanacaste, 
B-D, Lfnea Vieja. Coll. Gothenburg Ethnographic Museum, 64-16. Length of specimen 
C, 9 cm. 

etc.^" " With Brooks (p. 196) and others, we may assume that the "word 
cohoba may have meant snuff as well as the act of snuffing any powder. 
Pulverized tobacco seeds may have been mixed with the narcotic snuff inhaled 
by the medicine-men, and only the nicotian ingredient of this compound 
recognized by the Spanish observers." The Arawakan Jirara and Caquetio 
in N.W. Venezuela, tribes which according to Steward (1948: 21) had 
"certain specific resemblances to the Arawakan Taino of the Antilles," had 
medicine-men who "practiced divination with tobacco ash and communed 
with spirits while taking tobacco and a narcotic herb." The mixing of tobacco 
and yopo has been reported from many S. American tribes. 

Archaeological Evidence for the Use of Snuff 

If we consider the South American origin of the West Indian tribes, it is 
only natural that the close parallels referring to the snuffing complex in the 
West Indes should be sought in South America. I believe, however, that also 
the archaeologically found, often bird-shaped and bifurcated clay snuffers 
from Costa Rica, (Fig. 4), should be taken into account.^* These small clay 
snuffers with one or two tubes were, according to Doris Stone, "probably 
used for cojoia (Piptadenia sp.) or tobacco." ^® 

As always, the South American influence as far north as in Costa Eica 
is worth studying. To a possible explanation of the bird motif in the clay 
snuffers I will return later. Here I, want to refer to Fig. 5, where I, after 
Dr. Otto Zerries, can show an old bifurcated and nicely carved bird-shaped 
snuffing tube from South America. This highly interesting old specimen is 



33 Las Casas. 1909 : 445. 

34 See Wass^n and Holmstedt, 1963, fig. 6, and p. 24 ; also Wass^n, 1965, fig. 2, and pp. 25-26. 

3= Stone, Doris. 1958 : 16. Her figures 19 a, 6. Stone counts "snuflSng and the playing of flutes by 
medicine men" as "southern traits" in Costa Rica's cultures (p. 25). 
3« See Wass^n and Holmstedt. 1963 : 24. 



243 




Fig. 5. — Bifurcated snuffing implement of wood. Coll. Mus. f. Vdlkerkunde, Mannheim, 
"V. Am. No. 1894." According to Zerries, 1965, from BrazOian Guayana. Courtesy 
Dr. Otto Zerries. 

now in the Ethnographical Museum of Mannheim, Germany, where it has 
been observed and studied by Dr. Zerries, who has attributed it to the region 
of Brazilian Guyana.^^ The old snuffer in the German museum undoubtedly 
points to a South American background also for the clay snuffers in Costa 
Kica. 

In spite of many omissions and too hastily drawn conclusions, the study of 
Max Uhle of the bifurcated snuffing tube of bone that he found in 1895 at 
Tiahuanaco seems to be one of the first of a comparative interest for the use 
of snuffs among the South American Indians. A drawing after Uhle's illus- 
tration of the tube he found is shown in Fig. 6. According to Uhle (1898 : 1) , 
"the tube consists of the wrist or leg bone {metacarjms or metatharsis) of a 



Zerries, Otto. 1965: 185-193. In the same paper Zerries describes two more, richly decorated 
wooden objects from the Ethnographical Museum in Mannheim (numbers Am. 1987 and 1988), in 
the form of jaguars with bowls, which evidently have been receptacles for a powder. In the old 
museum entry it says "Gerat zuni Schnupfen," 'snuffing implement.' Zerries seeks the origin for all 
three in the lower R. Trombetas region. 



244 



young llama-like animal," . . . "and the bone has been cut off at each end, 
and while at the upper end a part of the shaft has disappeared, at the lower 
end, bifurcating naturally, only the distal articulations have been cut away 
and each part bored, so as to communicate with the main tube. The caliber of 
the former is and that of the latter 13/32 of an inch." 

Uhle reported from Tiahuanaco. Following him it has only slowly and 
after a long series of attempts at all sorts of more or less fanciful explana- 
tions, become evident that the many finds in the region of the former 
Atacameno in Argentina and Chile of wooden trays and their corresponding 
tubes, must be classified as paraphernalia connected with the taking of some 
kind of a snuff. Several earlier references have been mentioned in Wassen 
1965 (pp. 34-36 and p. 78) as well as in Wassen and Holmstedt (1963: 24- 
25) ; but I can perhaps best refer to the summary of the extensive literature 
presented in the archaeological thesis by A. M. Salas.^^ For the understand- 



^ Salas, Alberto Mario. 1945. Especially pp. 209-226, "Area de dispersi6n de tubos y tahletas." 




Fig. 6. — Naturally bifurcated snuffing tube of bone from Tiahuanaco. Drawing after 
Uhle's photographs in his publication from 1898. 



245 



ing of tlie snuffing complex in the Atacama region, important publications 
have recently been published. I want particularly to refer to the classificatory 
study by Lautaro Nunez,^® and the same author's references to the taking of 
rape during successive cultural periods in northern Chile.*" A small but 
interesting contribution is the paper by G. Mostny from 1956, in which she 
also refers to the tube from La Gonave, Haiti. Her paper from 1952, in which 
she offers a recapitulation of the various opinions regarding the finds of 
tabletas and tubos in Chile and Argentina, is also of high interest for the 
description (p. 8) of a grave find of a paricd tray with one sculptured and 
one plain tube. The tray was protected by a surrounding leather wrapping, 
which when taken away showed the handle in the form of a nicely carved 
condor. The circumstances prove that the Indians had taken much care in 
protecting this specimen when the owner got it with him in the grave. The 
sculptured tube in the same find shows, according to Mostny's description 
(p. 11) , a masked human being. 

In a new work from 1965, Father Gustavo Le Paige is also writing about 
several highly interesting finds of snuffing paraphernalia used in the Atacama 
region.*^ The list could easily be made much longer, but it was neither here 
nor in my study from 1965 my intention to present a complete catalogue 
of all such finds from a given area. My intention has been to underline the 
importance of archaeologically found snuffing paraphernalia in relation to 
the etlinographically known details. Scientifically it must be of an over- 
whelming importance to learn what kind of powder the Indians in the 
Atacama regions used, and what we can deduct about the ceremonial im- 
portance of the habit from the finds.*^ In Fig. 7-10 three wooden tablets 
and a tube from Chiuchiu and Argentina are shown from material kept 
in the Museum of the American Indian, New York City. Fig. 11, taken 
from Fig. 57 in Casanova's paper of 1946, shows interesting Argentine 
specimens with features often discussed in this work. 



3» Nunez Atencio, Lautaro. 1963 : 148-168. 

*i Xunez A., Lautaro. 1965. In this study the author has pointed out the use of snuffing tubes of 
bone among groups with a knowledge of both agriculture and pottery in the period he calls Early 
(0—700 A.D.), a period still without influence from the Tiahuanaco culture. During a Middle Period 
(700—1000 A.D.) the snuffing paraphernalia are continuously used, and a strong Influence from 
Tiahuanaco is observed. The use of snufiE trays and tubes continues during the Late Period 
(1000-1450 A.D.), when several local cultures developed after the influence from Tiahuanaco. 

" Le Paige, Gustavo. 1965. His work from 1964 has been quoted at the end of this paper. 

" I am most thankful to Dr. Lautaro Nunez A., Director of the Department of Archaeology of 
the Universidad de Chile, Zona Norte, Antofagasta, for his kindness in sending to me with a letter 
of October 7, 1966, samples of snufE powder archaeologically found and associated with a snuff 
tray from a pre-Incaic grave at the coast of Chile, near Iquique (Bajo MoUe) . The material has 
been forwarded to Prof. Bo Holmstedt, Stockholm, for analysis. We certainly need qualified analyses 
of archaeological snuff. Dr. Alberto Mario Salas (1945 : 222) indignantly criticizes Max Uhle, who 
once found powder associated with a snuff tablet at Calama, and concluded he had found a narcotic 
powder only from the fact that he and his assistant started sneezing after having blown the powder 
into the nostrils. Ricardo E. Latcham (1938: 133-135), started a discussion on which type of 
powder the AtacameSo could have been using. He suggested Piptadenia macrocarpa, "common in the 
subtropical valleys of Tucumfln and in the Chaco, and also used by the Calehaqufes," but imme- 
diately added that more probably it was some kind of tobacco. The Piptadenia macrocarpa should 
be the same as the Peruvian vilca. Latcham rejected the idea, suggested by Dr. A. Oyarziin, that 
Piptadenia peregrina had been used by the Atacameno. 



246 



Fig. 8. — Wooden snuff tray with human and feline motifs. Argentina. 3%" x 7)2", speci- 
men No. 15/1489. Photograph courtesy of Museum of American Indian, Heye Foundation. 



248 




Fig. 9. — SnufiF tube from Argentina. Sculptured motif seems to show a man holding a 
tube. Photograph courtesy of Museum of the American Indian, Heye Foundation. 
Specimen No. 15/2407. 

249 

262-016 0-67— 18 




Fig. 10. — Wooden snuff tray, 2>i' 



Handle probably personification of deity. 



Chiuchiu, ChUe. Photograph courtesy of Museum of the American Indian, Heye 
Foundation. Specimen No. 14/3741. 



250 



Fig. 11. — SnufEng paraphernalia, tablets and tube of wood decorated with zoomorphic 
and anthropomorphic figures. After fig. 57 in Casanova, 1946. Originals in Buenos 
Aires. 

In 1885, the Brazilian archaeologist Ladislau Netto when commenting 
upon the zoomorphic stone figures (often bird-shaped) found in the sam- 
haguis (shell middens) of Santa Catarina, Brazil, was long ahead of his 
time. With reference to the cavities observed in these figures (see Fig. 12), 
he took them to have served as a deposit for a vegetal powder, of exciting 
quality and ascribed with supernatural virtues.*^ This aspect is interesting 
and I must dedicate some time to it. 

The so-cajled antropolito de Mercedes^ a stone figure from Uruguay in 
the shape of a human being with a rectangular cavity on its front side (in 
the style of the Mexican Chacmool figures) has been labeled by Serrano 
(1939) as a tableta. This stone figure can be seen as Fig. 4 in the posthumous 
work by J. I. Munoa about the prehistoric peoples of Uruguay. The author 

" Netto, Ladislau. 1885 : 516-517. "Uma advertencia cabe-me aqui interpor sobre a palavra vaso 
que tenho dado a estes ambuletos. Alguns, na verdade, p6dem ter este nome, nao outros, por^m, que 
sao, a bem dizer, fetiches zoomorphos com uma peqflena e mal distincta cavidade no dorso, no ventre 
ou no flanco, onde' ao que presumo, o p6 vegetal excitante, a que attrlbuiam virtudes sobrenaturaes, 
era deposltado e sorvido. Quanto aos vasos fetiches ou zoomorphos, muito 6 de crer que n'elles 
fossem deposltadas substancias varias com attribuigao de eguaes preconceitos, ou que servissem 
para pulverisar as folhas de alguma planta sagrada ou qualquer outra materia destinada a cere- 
monias religiosas." 



251 



Fig. 12. — Bird-shaped so-called zoolithos from sambaqms in Santa Catarina, Brazil. 
Drawings after pi. VI in Netto's publication of 1885. 



252 



shows how the nicely sculptured stone specimens (Utos) in animal form, 
and often birds {'"'■que -figwan comv/nmente aues") belong to a stone- working 
culture of the (later) Tupi-Guara,ni region of southern Brazil (Santa Ga- 
tarina and Rio Grande do Sul) and the eastern parts of Uruguay.** 

These special stone figures in human or animal form (birds, fishes, etc.) 
with cavities have been classified by Munoa (p. 16) as '■Hahletas shamdnicas 
para aspirar parica'\ and included in what Serrano used to call the Guayana 
Culture, which also goes under the name of the Rio Grande Culture. The 
Guayana, according to Metraux (1946: 445), should be counted with the 
Caingang, a designation for several "non-Guarani Indians of the States of 
Sao Paulo, Parana, Santa Catarina, and Rio Grande do Sul, Avho previously 
were known as Guayana, Coroado, Bugre, Shokleng, Tupi, Botocudo, etc., 
but who are all linguistically and culturally related to one another and 
form the southern branch of the Ge family." Nothing, however, seems to 
indicate that the Caingang were the masters of the stone objects mentioned 
here. On "Narcotics", Metraux (1946: 469) says only that "a great many 
stone pipes have been found in the Caingang area — ^a puzzling fact since 
smoking has not been observed among the Indians." This, however, was 
contradicted on the following page, where he says that "the Caingang 
shaman consults spirits at night, puffing his pipe until he is surrounded by 
a cloud of smoke." 

But, as these litos evidently are of interest as possible ceremonial receptacles 
for snuff, to which culture do they really belong? The question seems open to 
discussion. Munoa assigned them to a first wave of Indians in Uruguay, the 
Sambaguianos. Serrano placed the Utos in a pre-Tiahuanaco period or 
Middle Samtiqui phase.*^ The culture is said to have come from the north. 
Vidart has on p. 61 of his edition of Munoa 's work dated the culture which 
left the shamanistic stone tablets {Has tabletas shamdnicas en piedra'"') at 
3.000 B.C., but no reasons for this very early dating have been given. For my 
own part I should prefer to consider the litos in southern Brazil and eastern 
Uruguay in. some way related to the finds from the Amazon region (the 
Gontas^ muiraquitas, etc. of the "Rio Trombetas," see Wassen, 1965 : 34) , per- 
haps so that a specialization in a craftsmanship connected with a ceremonial 
use of psychotomimetics has some center of origin until now unknown ; how- 
ever, within the Amazon region. 

In Wassen, 1965 : 34, the Mercedes figure from Uruguay has already been 
mentioned following a presentation of the '"''idolo'''' or '•'•conta)'' from the Rio 
Trombetas region with its "Alter ego" motrf, and its carefully hollowed 
out cavity on its back (Fig. 13) as having been used for holding some kind 
of a psychotomimetic snuff. When publishing this specimen from the Gothen- 
burg Ethnographic Museum, I saw its "beautiful craftsmanship reflected in 
the snuff boards with animal motifs used by the Cashuena, and earlier also by 

«MuSoa, Juan Ignacio. 1965 : 14—19 (edition and notes by Daniel Vidart). I liave not said that 
the Tupi used snuff of the kind discussed here. Alfred Metraux (1948 a: 127) has not mentioned 
the use of paricA, but that of tobacco smoking, "one of the favorite pastimes in daily life as well as 
on ceremonial occasions." He also points out that "stone pipes, found in several points of the 
Brazilian coast, perhaps belong to another culture anterior to that of the TupJ." 

« Munoa, ed. by Vidart. 1965. P. 16 and map on p. 12. 

253 



Fig. 13.- — Stone figure with cavity. Sucuruju, R. Trombetas, Brazil. Gothenburg Ethno- 
graphic Museum, Coll. No. 25.12.1. Height 17.5 cm. 

other Amazonian tribes." I could in 1965 also show a direct parallel to its 
artistic motif, a man being dominated by a jaguar on his back, when referring 
to a detail of a snufiing tube from Puna de Jujuy published by Ambrosetti in 
1908 (see Wassen, 1965, Fig. 7, and this work Fig. 14) . The figure shown in 
Fig. 14 is by no means a single example. In Fig. 15 we see the same motif, that 
is a jaguar dominating and above a human representation, on a fragment of a 
wooden snuffing tube found together with a tray ^vith handles in the form of 
two human figures in an excavation in the Antigal de Cienega Grande of the 
Puna de Jujuy, Argentina, and published by Salas. (1945: 205-208, Figs. 
86-89). 

As mentioned in Wassen 1965 : 36, Dr. A. A. Gerbrands in 1955 related the 
carved stone objects from lower R. Trombetas to the Maue Indian sculpture 
in wood. We can safely connect the paHcd trays with two human figures 
found in Argentina and Chile, with the beautiful Tucano parted tray in the 
Oslo University's Ethnographical Museum analyzed in 1965.*^ 

The Jaguar, as a powerful and dangerous animal, has certainly always 
played a very important part in Indian beliefs as reflected in their ceremonial- 

'0 Wassen. 1965 : 68-80, and figs. 31-36 and 38-39. 



254 



ism. It is thus not without reason that we in the American Museum of Nat- 
ural History, New York, find the Jaguar repeatedly represented in a series of 
snuff tablets and tubes originating from the "Gentilar de Caspana", north 
Chile. 

In one special case, the comparison that can be made between ethnogra- 
phically known snuff tablets in the Amazon region and a wooden snuff tray 
with feline head archaeologically found in Atacama, Chile, is absolutely 
surprising. For this I refer to Fig. 22 in this work, with kind permission 
published from a photo received from the Museo de Arte Precolomhino in 





255 



Fig. 15. — Section of snuff tube from Cienega Grande, Puna de Jujuy, Argentina. After 

Salas. 

Montevideo.*^ I am in this case nearly prepared to accept the Atacaman tray 
as a direct trade piece from the Amazon region. The late Dr. Stig Ryden, in 
his work on the archaeology of the Rio Loa region, was specifically interested 
in the trade relations between the Atacameno and the lowlands in the east.** 

If we now look for other archaeological finds of snuffing paraphernalia in 
South America, the snuff tablet and its tube reported by Dr. J. B. Bird from 
near the Huaca Prieta, Chicama Valley, Peru, is the most interesting, as it 
appears in a very old culture sequence.*® According to information received 
from Dr. Bird following my visit to New York in September, 1966, it is the 
question of a "snuff tablet of whalebone, Chicama Valley, Peru, near the 
Huaca Prieta. Test 4, House 3, associated with skeleton 99.1/880, the snuff 
tube 41.2/4722 a, b., and a broken jet mirror. The burial was made during 
the period when Guanape pottery was in use. (The oldest pottery known in 
this area). Estimated Age, c. 1200 B.C.; oldest known tablet (as of 1966)." 
(Letter of Nov. 2, 1966). See Fig. 23 for this specimen. 

Dr. Bird has also had the kindness to inform me about a find of a snuff 
tray of wood collected by Mr. G. S. Vescelius in 1959, "from a Late Inter- 

" See plate 38 in "Arte PrecolomMno, Coleccidn Matto," Museo de Arte Precolombino, Montevideo, 
1948. 

" Ryd^n, Stlg. 1944. See his summary, pp. 20&-212, also the discussion of the origin of the 
material of a leather cuirass made of the skins of alligator and monkey (pp. 115-116). According 
to Wendell C. Bennett (1946 : 603) the "AtacameQo were great traders." 

" Bird, Junius B. 1948 : 21-28. Also Wass^n and Holmstedt, 1963 : 25, and Wass^n, 1965 : 79-80. 



256 



Fig. 16. — Snuff tray with feline motif and corresponding tube. Atacama. Specimen 
courtesy of the Museo de Arte Precolombino, Montevideo. 




Fig. 17. — Both sides of whalebone snuff tablet and its corresponding tube. Specimens 
discovered by Dr. Junius B. Bird near the Huaca Prieta, Chicama Valley, Peru. Oldest 
known tablet (as of 1966). Coll. and courtesy of the American Museum of Natural 
History, New York. Specimen 41.2/4721 (tray), 41.2./4722 a, b, bird and fox bone 
snuff tube, found with the tray. 

257 



mediate burial at Santa Maria Miramar, a site near Mejia, on the Peruvian 
coast about 20 kilometers south of Mollendo. There are tvro phases (one Inca, 
the other immediately pre-Inca) represented at this site. The burial dates 
from the earlier, pre-Inca phase. Associated with the snuff tray in the grave 
were a miniature raft with its paddle, a bagfull of model harpoon f oreshafts, 
and a spindle with rectangular whorl."' Various specimens in the collections 
of the American Museum of Natural History, N.Y., are shown in Figs. 16-21. 




Fig. 18. — Both sides of four snuff tablets of wood in the American Museum of Natural 
History, New York. Photographs courtesy of A.M.N.H. A, 41.0/8754, Cemetery at 
Chiuchiu, Chuquicamata, ChOe; B, 41.0/8746, same data; C, 41.0/8911, Grave site 
near San Pedro, Chuquicamata region. North Chile; D, 41.0/8912, same data as C. 



258 



Fig. 19. — Nine snuff trays of wood from Chile. Coll. and courtesy of the Americarx 
Museum of Natural History, New York. Eight specimens from Cemetery at Chiuchiu, 
one from Puntas Tetas near Antofagasta (bottom row, third from left). 




Fig. 20. — Four snuff tablets of wood from Chile. Coll. and courtesy of the American 
Museum of Natural History, New York. From left: 41.0/8750, Cemetery at Chiuchiu: 
B/9568, "Taken from child's grave," Juan Lopez Bay, near Antofagasta; 41.0/8964, 
Cemetery about 3 km. from Chiuchiu, and 41.0/8751, Cemetery at Chiuchiu, Chu- 
quicamata. 



259 




Fig. 21. — Snuff tubes of bird bone and bone and wood. Chile. Coll. and courtesy of the 
American Museum of Natural History, New York. These specimens come from Chiu- 
chiu, Cobija and Lasana ruin, near Chuquicamata. 

From the Huaca Prieta find, it is evident that snuffing paraphernalia were 
in early use in the Peruvian high culture area. I have in my book from 1965 
(p. 80) referred to W. von Hagen's statement that "there is no doubt that 
the coastal yuncas, as their contemporaries, the Andean dwellers, had a wide 
knowledge of drug-yielding plants." Specific trade routes were mentioned : 
"Huancabamba had extensive trade alliances with the coast people. It was 
also a trade-axis for the jungle; a route less than sixty miles ran from the 
mountains about Huancabamba down to Jaen, near to the Rio Maranon, one 
of the tributaries of the Amazon rivers system." ^° It was, according to von 
Hagen, the milieu of the widely spread and trading Shuara (or Jlvaro). 
Among various articles traded by these Indians, von Hagen (p. 150) espe- 
cially mentions several narcotics, among them ^^niopo snuff (which was in- 
haled into the nose through the shank bone of the Oil-bird.") In this con- 
nection it is tempting to refer to a painting on a Mochica vessel from Period 
V (c. 600-700 A.D.) published by Alan R. Sawyer." The vessel, which 
belongs to the Nathan Cummings Collection in the Metropolitan Museum of 
Art, New York, shows according to Sawyer an "ornately caparisoned war- 

60 Hagen, Victor W. von. 1965 : 149. 
M Sawyer, Alan R. 1966 : 46. 



260 



rior-bird" which is "collecting the narcotic fruit of the uUvhclio tree, which 
grows in the highlands." 

Following my publication of the claysnuffers from Costa Rica, Doctors 
Clifford Evans and Betty J. Meggers of the U.S. National Museum in a letter 
of March 24, 1966, raised the question if the so-called "pottery spoons from 
Marajoara Phase" published by them as plate 81 in Bulletin 167 of the 
Bureau of American Ethnology might be a snuff device. "These were ruled 
out as smoking pipes because of two factors; one, was position of the hole 
in all but one, and in that one, there was no indication whatsoever that it 
had been used for a pipe. Since they don't occur in the culture we use the 
term that has been used by others, namely pottery spoons. If they are actually 
used in snuff taking it would move the distribution down to the mouth of the 
Amazon and at a earlier time zone than the rest of your region." (Letter of 
March 24, 1966). The possibility that these objects served as some kind of 
snuffing paraphernalia should perhaps be taken into account. In the general 
form these clay specimens very much resemble the mortars of fruit shell 
used for preparing the paricd snuff in parts of the Amazon region.^^ 

■^^ Comp. for instance the object, pi. Sib, in the publication by Meggers and Evans (1957) with 
the mortar, fig. 25 (p. 60) in Wass^n 1965. 




A B C D E: F 6 

Fig. 22. — SnufT tubes from Chile. Coll. and courtesy of the Museum of Natural History, 
New York. A, B/4452, bone and wood, Arica; B, 41.0/8742, wood, Cemetery at Chiu- 
chiu; C, 41.0./8994, wood, Chiuchiu; D, 41.0./3415, wood, Chiuchiu; E, 41.0.8739, 
wood. Cemetery at Chiuchiu; F, 41.0.8740, wood, metal at nd, Cemetery at Chiuchiu; 
G, 41.0.8741, wood. Cemetery at Chiuchiu. 

261 




Fig. 23. — SnufF tube and thorn bundles from snuff tubes. Coll. and courtesy of the 
American ^Museum of Natural History, New York. The tube, 41.0/1713 J, from Chiu- 
chiu, Chile. The bundle of seven thorns beside the tube was|found in the tube. Wrap- 
ping is sinew. The other thorns belong to 41.0/8662, all unassociated with original tubes. 
Cemetery at Chiuchiu, Chuquicamata, Chile. 



The map in Fig. 24 shows the distribution of archaeological finds which 
definitely, or in some cases possibly, should be related to the taking of psy- 
chotomimetic snuffs. 

Ethnographical Data About the Use of Snuffs 
in South America 

The first thing prepared for this chapter has been the distribution map 
in fig. 25 with its legend. In this map tribal names and data about the snuff- 
ing of paricd or yopo as well as epena snuffs as presented in Zerries (1964, 
map 10, text pp. 85-93) have been incorporated with the ethnographic in- 
formation presented in the map in "Wassen, 1965, p. 13. The data given by 
Cooper (1949, map 10, pp. 536-537) have also been used, as have some of the 
information from Colombia presented in the paper by Xestor Uscategui M. 
(1959). As far as I understand the final result must give a fairly complete 
picture of the distribution of psychotomimetic snuffing among the South 
American Indians according to published reports. 



262 



Fig. 24. — Distribution of Archaeological Finds. See Legend. 



Legend to Map in Figure 24- 



1. Haiti. Finds connected with the use of cohoba. 

2. Puerto Rico. Stone cemi with platform on top. 

3. Finds of clay snuffers in Costa Rica. 

4. Mochica Culture, N. Peru. Painted motif on a pottery vessel supposed to show the 
collecting of the narcotic fruit of the ullucho tree (?) . 

5. Whalebone snuff tablet and bone tube. Huaca Prieta, Chicama Valley. Fig. 17. 

6. Uhle's snuffing tube of bone from Tiahuanaco. Fig. 6. 

7. Pre-Inca phase wooden snuff tray from Santa Maria Miramar, south of Mollendo. 

8. Finds of snuffing paraphernalia at Chiuchiu, Chile. 

9. Finds from the Changos, Coast of Antofagasta, Chile. 

10. Finds from the Atacama region. 

11. Finds from the Puna de Jujuy, Argentina. 

12. Province of C6rdoba, Argentina. 

13. Stone figure (17.5 cm. high) with cavity on its back. Sucuruju, R. Trombetas, Brazil. 
Gothenburg Ethnographic Museum, Coll. 25.12.1. 

14. So-called pottery spoons from the Marajoara Phase. (?) 

15. Zoomorphic stone figures {litos) from S. Catarina and R. Grande do Sul, Brazil. Fig. 



12. 



16. 
17. 



Finds of litos in Eastern Uruguay. 
The antropolito de Mercedes, Uruguay. 



263 




264 



Legend to Map in Figure 25. 



1. Highland Chibcha and Tunebo, Chibcha neighbors on the east. Piptadenia snufiF, see 
Cooper, 1949:536. According to Oviedo, Historia etc., vol. IV: 607 (Madrid 1855), 
yop was a "yerba de adivinacion, usada por los mojas 6 sacer dotes del sol en las voiles de 
Tunja y Bogota. {Lengua de Nueva Granada) ." A reduced number of Tunebo are still 
found in "the humid jungle regions in the southwestern part of the Comisaria de 
Arauaca," Colombia (Uscategui, 1959:298-299). Same author, p. 299: "The custom 
of snuffing yopo was acquired probably from their Arawak neighbors in Venezuela 
and Colombia." A knowledge of nutmeg (at least for trade purposes) existed among 
the Tunebo of the early 18th century. According to Gumilla (1744:307) "el Padre 
Pompeo Carcacio, que fu6 Missionero de los Tunevos muchos anos, nos assegur6, que 
en su tiempo traian aquellos Indios Nuez moscada, tan parecida en todo d la que traen 
del Oriente, que no se podian distinguir unas nueces de otras; pero yo no la he visto, 
ni s6 que oy la saquen." 
2-3. Caquetio and Jirajara, extinct tribes. The medicine-men took tobacco and a nar- 
cotic herb when they practised divination and communed with the spirits. Cf . Wass6n, 
1965:105. Probably Piptadenia snuffers. 

4. Inyeri, Arawak Indians of Trinidad, yopo snuffers (Zerries, 1964:88, and Cooper, 
1949:536, "early Contact Indians of Trinidad." Castellanos, 1950:93: (in "canto 
cuarto") , " t/no toma tabaco y otro yopa para poder saber lo venidero." 

5. Palenque and Piritil. Two Carib tribes (Zerries, 1964:88). According to Herndndez 
de Alba, 1948:411, "the Palenque, Piritil and Sdliva shamans also used "yopa" for 
divination." 

6. Waica, Samatari, Surdra, Sanemd and Pakiddi, subgroups of the Yanoama, southern 
Venezuela. These Indians use snuff piepared from Virola sp., the snuff now inter- 
nationally known as epena (the Waica name). See information and references in 
Wass6n and Holmstedt, 1963:8, and Wassen, 1965:98-99. Also, Holmstedt, 1965. 
According to Zerries, 1964:85, the Waica should also use Piptadenia peregrina. 

7. Karime (or Shudri), Indians culturally related to the Waica. According to G. Salath6, 
quoted in Wassen, 1965:99, and in Wassen and Holmstedt, 1963:14, these Indians 
prepare a snuff made of leaves from a small plant called kokoime. A 30 cm. long 
straight tube is used. Another person blows into the nostrils. 

8. Araraibo, Indians at the upper Cauaburi River, an affluent of R. Negro, border 
region between Venezuela and Brazil. Visited by Georg J. Seitz, see his book from 
1960. Information on the powder prepared of material from Virola sp. has been 
summarized in Zerries, 1964:85-86. Evidently closely related to the Samatari (Seitz, 
1960:306, has published a short "Araraibo-Xamatari Word List"), or a Waica group. 

9. Paravilhana, Carib Indians. Martins, 1867:631, has reported the use of paricd powder 
from Mimosa acacioides. Cf. Zerries, 1964:87. 

10. Yecuand-Makiritare, Carib Indians of southern Venezuela. See the translation of 
Th. Koch-Grtinberg's description of the use of the hakudufha, a "bark of tree"-powder 
from these Indians in Schultes, 1954:245, also quoted in Wassen, 1965:97. According 
to Schultes, an identification of the unusual narcotic Virola-snuS with the powder 
mentioned by Koch-Grunberg seems almost certain. Dr. Helmuth Fuchs (letter of 
March 9, 1962, quoted in Wass6n, 1965:97), has described a'ku:duwha as a snuff 
powder with ingredients which botanically can be shown to have come from Pipta- 
denia peregrina, or another Piptadenia. There are also other ingredients from a tree, 
probably Virola sp. See also discussion in Wassen and Holmstedt, 1963:10-12. Cf. 
Zerries, 1964:87-88. Cf. No. 24. 

11. Yabarana. Carib Indians, related to the Makiritare. Johannes Wilbert, 1963:133, 
mentions the use of tobacco, yopo, and cdpi among the Yabarana (Wassen, 1965:20). 
Zerries, 1964:88, quoting a paper by Wilbert from 1959, mentions that the Yabarana 
should obtain their yopo from a liana (?), and a tablet and Y-formed snuff t\ibe 
are used. 

12. Piaroa, Indians of the Salivan Family, Orinoco- Ventuari territory, see Wass6n, 
1965:103. According to Wilbert they use yopo, a strong "tabaco-rape," prepared 
from the seeds of Piptadenia sp. The powder is passed around in a round tray with 

265 

262-012 0-67— 19 



Legend to Map in Figure 25 — Continued 

handle in the form of a fin (of a fish) and Y-shaped tubes of bird bone are used. Ac- 
cording to J. J. Wurdack, bark of Lecythidaceae is burned and the ash added to the 
yopo of Piptadenia seeds. Quotation in Wassen, 1965:103. 

13. Puinave. Indians at the lower Infrida River, southeast Colombia and adjacent terri- 
tory of Venezuela. Several quotations in Wassen, 1965:99-100. Dr. R. E. Schultes, 
1954:248, has repeatedly observed the preparation of "a violently toxic snuff" among 
the Puinave. This snuff is prepared from an exudation of Virola calophylla and Virola 
calophylloidea. 

14. Kuripako, Arawak Indians of the Guainfa River. Schultes has described a narcotic 
snuff prepared of Virola sp. Quotations in Wassen, 1965: 100. 

15. Achagua, once widely distributed Arawak-speaking Indians in Venezuela and eastern 
Colombia. Herndndez de Alba, 1948:409, says that "the Achagua used a snuff made 
of the narcotic powder of certain leaves called "niopa" or "yopa." Two Indians took 
this snuff simultaneously; with two crossed bird bones, each blew it into the other's 
nose." Cf. No. 19 in this list. Also Zerries, 1964 :89. Sven Lov4n, 1935:387, says that 
yopa "is an Achaguan name." For a full quotation of the prognostication combined 
with the taking of yopo powder from the relation written by the Jesuit missionary 
Juan Rivero in 1736, I refer to Wassen, 1965 : 19. "A nasal secretion from the right 
nostril signified success, from the left meant failure, and from both was an indetermi- 
nate sign." 

16. Guahibo, Chiricoa, Saliva. Several references to these Colombian- Venezuelan Llanos 
tribes in Wass4n, 1965:104. The Guahibo and Chiricoa men "invariably carried a 
shell or a jaguar bone containing parica. These tribes were said to carry the habit 
of parica snuffing to extremes not found among the neighboring tribes" (Kirchhoflf, 
1948:455). Cf. Zerries, 1964:89. 

17. Piapoco, snuffers of Piptadenia. See Cooper, 1949:536. 

18. Guaupe and Sde, Arawak Indians. Zerries, 1964:89, has quoted Kirchhofif's article 
on these Indians in vol. 4 of the Handbook of South American Indians (Washington: 
1948), p. 385-391, about the taking of "coca (yupa), and tobacco." The probably 
Arawak Indians once lived "in the southernmost section of the Venezuelan-Colombian 
llanos," the Guayup6 "also in large parts also inhabited the dense rain forests of the 
Andean sloops" (Kirchhoff, p. 385.) 

19. "Ouitoto" Indians of the upper Yapurd River. See Zerries, 1964:91, and the discus- 
sion of the crossed tubes for snuffing among the "Ouitotos" of Dr. Crevaux in Wassen, 
1965:87-90. It is a possibility that herndndez de Alba when formulating the state- 
ment about the Achagua (see No. 15 in this list) has been influenced by the drawing 
and text in the work of Crevaux. No source is given for the statement about the 
Achagua. Until such a reliable source has been presented, I prefer to consider the 
often published drawing in the publications of Dr. Crevaux of two Indians using 
crossed snuffing tubes, as dubious. 

20. Taiwano. Indians of the R. Kananari, Comisaria del Uaup^s, Colombia (Cerro 
Isibukurf). According to Schultes, 1954:242, they use a narcotic snuff of Virola. 

21. Otomac. Tribe in the Venezuelan Llanos, between Orinoco, the Apure, and the Meta 
Rivers. According to Paul Kirchhofif's paper on these Indians in vol. 4 of the Handbook 
of South American Indians, pp. 439-444 (Washington, 1948), "Otomac shamans, 
under the influence of nope, predicted the future." Humbolt was a witness of Otomac 
snuffing the powder of Acacia niopo seeds with lime as an ingredient. As he is one of 
the very few who really gives a description of the preparing of the snuff, I quote 
from the "Personal Narrative" (Humbolt and Bonpland, 1818-1929, vol. V: 66 1-663): 
"The Otomacs are a restless turbulent people, with unbridled passions. They are not 
only fond to excess of the fermented liquors from cassava and maize, and of the palm 
wine, but they throw themselves into a peculiar state of intoxication, we might almost 
say of madness, by the use of the pwoder of niopo. They gather the long pods of 
mimosacea, which we have made known by the name of acacia niopo, cut them into 
pieces, moisten them, and cause them to ferment. When the softened seeds begin to 
grow black, they are kneaded like a paste, mixed with some flour of cassava and lime 



266 



Legend to Map in Figure 25 — Continued 

procured from the shell of a helix, and the whole mass is exposed to a very brisk fire, 
on a grate of hard wood. The hardened paste takes the form of small cakes. When 
it is to be used, it is reduced to a fine powder, and placed on a disk five or six inches 
wide. The Otomac holds this disk, which has a handle, in his right hand, while he 
inhales the niopo by the nose, through a forked bone of a bird, the two extremities 
of which are applied to the nostrils. This bone, without which the Otomac believes 
that he could not take this kind of snuff, is seven inches long: it appeared to me to 
be the leg bone of a large sort of the plover (ichassier). 1 sent the niopo, and all this 
singular apparatus, to Mr. de Foucroy at Paris." According to Rosenblat, (1965:272) 
nothing of all this is now remembered among the Llanero population said to be de- 
scendants of the Otomac. Also, their language has gone. 

22. Cashuena. Indians of the Carib Family on the Casuro (Cashorro) River, a tributary of 
the middle Trombetas River, Brazil. From this tribe Protdtasio Frikel has described 
a mori snuff, which can be made "simply of tobacco" or of other ingredients among 
which paricd is mentioned. A full quotation is found in Wass6n, 1965 : 103, and also in 
Wassgn and Holmstedt, 1963:21-23. The snuff mentioned by Mr. Gottfried Poly- 
krates seems to originate from Piptadenia seeds. Details in Wass6n, 1965:103. 

23. Tuyuca and Bar a, Tucanoan tribes on the upper Tiqui6 River. As quoted in Wassen, 
1965: 100, the use of paricd or niopo has been mentioned by Whiffen from the Tuyuca, 
and Zerries, 1964:90, refers to Koch-Griinberg's statement about the use of a snuff 
from Mimosa acacioides Benth. among both tribes. 

24. Cuheo, one of the Eastern Tucanoan tribes at a section of the Uaup6s River. Schultes, 
1954:242, describes the Cubeo as users of Virola snuff. Of. Wass6n, 1965, about their 
use of Banisteriopsis caapi. According to Goldman, 1948:796, "the shamanistic 
novice spends a month learning the art from at least two professionals. He obtains 
tree resin, dupa (Tucano), and inhales it in a powdered form for 4 days." Bodiger, 
1965:151, refers this to the Cubeo novices, and mentions also Koch-Griinberg's ex- 
planation of the word dupa as meaning small white stones used for sorcery. In the 
meaning tree resin which is inhaled as a powder, the word is of direct interest through 
the term hakudufha, offered us by Koch-Grunberg from a linguistically mixed region 
with contact zones between several language families. 

25. Tucano. In this word an important group of Indians of the Uaup6s and Papuri Rivers 
are included. Schultes has in 1954 reported the use of Virola snuff, and Uscategui 
has in 1959 mentioned a mixture of Virola and Theobroma subincanum powders. 
Mr. Georg J. Seitz has photographed a Tucano medicine man grinding the dry crust 
of evaporated Virola calophylloidea exudation to snuff powder with a stone. The 
photos were taken by him at Tapuruquara, upper R. Negro, Brazil, in 1965 (see 
Wassen, 1965:100-101, also p. 73). In Wassen, 1965:68-76, it has been demonstrated 
that the Tucano used very fine sculptured snuff trays in earlier days. Uscategui, 
1959:294, remarks that the Tucano commonly use the Tupl-Guarani loan-word 
pa-ree-kd (paricd) for the snuff prepared from "the blood-red resin of certain species 
of the myristicaceous tree, Virola, especially V. calaphylla and V. calophylloidea." 

26. Barasana, Makuna, Yahuna, Yabahana, Menimehe. Zerries, 1964:90-91, has men- 
tioned that Koch-Grunberg found the same snuffing pa^apherna'ia among the Tu- 
canoan tribes (or groups) Makuna, Yabahana and Yahuna at the lower Apaporis 
River, as he had found among the Tuyuca and Bard (No.23) at the upper Tiquie 
River. Schultes found Barasana and Makuna Indians living together at the R. 
Piraparand, both tribes snuffers of Virola (see Wassen, 1965:101). This drug seems 
also to be used among the Yakuna and Yabahana. Whiffen has listed the Arawak 
Menimehe at the Yapurd River as users of a narcotic snuff. See Zerries, 1964:91. 

27. Pase, Juri and Uainuma, once important Arawak tribes south of the Yapurd River, 
noted as paricd snuffers and also listed among such tribes by Zerries, 1964: 91, as 
also by Wassen, 1965:66, according to Metraux. The Pas6 have been mentioned in 
Wassen, 1965:68, as one of the Brazilian tribes called "black-faces," as they used 
a special tribal identification, the so-called malhas. They have been reported as 
excellent wood-carvers. 



267 



Legend to Map in Figure 25 — Continued 

28. Omagua. In Wass^n, 1965 : 83, there is a detailed description of this Tupf tribe through 
Father Samuel Fritz, who in 1701 had to calm an uprising in the Settlement of San 
Pablo. Pots with powdered curupd were found, "with which to deprive themselves 
of their senses, so as to carry out any evil deed without compunction." This ma- 
terial was all consumed with fire upon orders given by Father Fritz after his Mass. 
Metraux has stated that both the Omagua and Cocama, also a Tupf tribe further 
west, "inhaled powdered curupa leaves (Mimosa acacioides) , to which they ascribed 
great therapeutic and magical powers." According to Metraux, the curupd "was 
blown into the nose through Y-shaped tubes or, with the help of small rubber sy- 
ringes, administered as a clyster which provoked agreeable visions." Quotations in 
Wass6n, 1965:83. Zerries, 1964:92, seems to doubt the use among the Cocama. 
According to La Condamim's Relation, etc. from 1778 (quoted in Wass4n, 1965:84) 
the word curupd for Piptadenia should originate from the language of the Omagua. 
Monteiro de Noronha, writing in 1768 about the Omagua, which he calls Umaud or 
Cambebas, "Flat Heads," criticizes La Condamine for his statement that the curupd 
intoxication should last 24 hours, and corrects it to "apenas dura tres horas" (Mon- 
teiro de Noronha, 1862:58). The same author adds that the Cambebas used the 
juice from the bark of the manacd, which has been identified with Brunfelsia hopeana 
Benth. of the Solanaceae family. 

29. Tucuna. As follows from the analysis in Wassen, 1965:82-83, these Indians who 
now only snuff tobacco, are known to have been using paricd snuff in earlier days 
for their ceremonial snuff called ka'jvi. The very important snuff tray found in the 
Oslo University's Ethnographical Museum and published in Wassen, 1965, fig. 41, 
has by an ethnographical analysis been shown to come from the Tucuna, and to 
represent the prego monkey demon. See Wassen, 1965:80-86. 

30. Piro. One of the Arawakan-speaking tribes of the headwaters of the Ucayali and 
Madeira Rivers, by Julian H. Steward and Alfred Metraux counted as a primitive 
Montana subgroup. The use of the seeds of Acacia niopo has been reported among 
the Piro by William Curtis Farabee in 1922. For the hunter and his dog, see Wass6n 
1965:94. Cf. No. 31 in this list. 

31. Catawishi, Indians of the river Puriis. Spruce has in 1874 reported from these Indians 
that they used to absorb paricd through a bent tube, and also that they administered 
an injection of paricd to dogs, thus a confirmation of that stated from the Piro. Full 
quotation in Wassen, 1965:96. See also Cooper, 1949:547. 

32. Mura. For the once much feared Mura Indians of the Madeira River the use of 
paricd must have been of outstanding importance. This is clearly demonstrated in 
the descriptions quoted in Wassen, 1965:37. The roasted seeds of the paricd tree 
were taken either as a snuff or an enema. The snuff was blown into the nostrils by 
means of bone tubes. The effects of the drug consumption in this tribe have been 
drastically described. Schultes has warned that we cannot be absolutely sure that 
the snuff used by the Mura and Mau6 was prepared from Piptadenia, as a botanical 
consideration must be kept in mind. Cf. Wass6n, 1965:23. 

33. Maue. These Central Tupi Indians were formerly famous for their paricd, which they 
do not use any more (see Nunes Pereira, 1954:71). Mimosa acacioides is given as the 
source. They have also been carving very nice specimens of snuff trays, now kept in 
several museums. See the description in Wassen, 1965:39-63. 

34. Mataco. Indians of the Gran Chaco, among whom the shamans have been reported to 
use snuff from the seeds of cebil, that is Piptadenia macrocarpa. Information collected 
by Metraux has been quoted in Wassen, 1965:29. 

35. Lule. Extinct Indians in western Chaco, Argentina. Metraux has mentioned the Lule 
together with the Mataco. An old information from the Lule comes from Pedro 
Lozano (1733), who states that cevil was blown into the nostrils by a small tube in 
order to provoke rain when necessary for their cultivations. Full quotation in Wassen, 
1965:11-12. 

36. Comechingones. Cooper, 1949:536, has listed the extinct 16th-century Indians 
around C6rdoba, Argentina, among those taking Piptadenia powder. See Zerries, 



268 



Legend to Map in Figure 25 — Continued 

1964:93, for further references to the use of cehil and/or wilca in the southern region, 
where also the Zanavirones are reported to have used it. Max Uhle, 1898:9, has quoted 
vol. II of the "Relaciones Geogrdficas de Indias, Peru", p. 152, from a report dealing 
with "la Ciudad de C6rdoba," where the Indians spoke comechingona and zanavirona: 
"Toman por las narices el sebil, ques una fruia como vilca; hdcenla polvos y hibenla por 
las narices." Uhle comments (p. 9): "The curious expression, they drink the powder 
with the nostrils, means without doubt that the Indians took the powder by means of 
an instrument like a tube. Concerning the word sebil, Napp (The Argentine Republic, 
1876, p. 114) tells us that sebil is in Argentine the name of the Acacias. Now, the fact 
that Humboldt originally pointed out the niopo tree as a species of Acacia by mistake 
and von Martius called it Mimosa acacioides proves that Piptadenias and Acacias 
have sometimes been confounded. We know, further, that Piptadenia trees of the 
variety niopo are also common in eastern Bolivia and the Argentine (for instance 
Piptadenia macrocarpa, in the province of Tucuman) . As the bark of the curupau tree, 
which from its name and general description may be a niopo tree, serves, according 
to Cardus, to tan hides in eastern Bolivia, so in like manner the bark of sebil is used 
to tan hides, as I noted, in the environs of Tucuman. All this leads to the conclusion 
that the tree, from whose seeds the powder was made, is related to niopo, and a sci- 
entific determination may perhaps show it identical with niopo. The custom of snuff- 
ing sebil in the environs of Cdrdoba was, therefore, derived from another part of the 
continent, where snuffing niopo was practiced." The conclusion by Uhle must be con- 
sidered as very important also when we take the distribution of paraphernalia into 
account. 

37. Tupari, Guaratdgaje, Amniapd, and other tribes in western Brazil, in the R. Branco 
region and on the Mequens River, affluents of the Guapore River. Cooper, 1949 : 536, 
refers to "the upper Guapor6 tribes." Zerries, 1964:91, has, according to a report of 
Dr. Etta Becker-Donner, Vienna, added the Aikand or Hauri, as their medicine-men 
use a snuff of Piptadenia peregrina mixed with bark ashes. Dr. Becker-Donner has 
also reported the use of such powder among the Salamay in the same region, as 
quoted by Zerries, 1964:91. The most valuable information from the whole Guapore 
region as regards snuffing has been given by Dr. Franz Caspar from the Tupari. I 
refer to his book from 1952, and his manuscript from 1953, both quoted in Wass6n, 
1965:102, and as regards the snuffing tubes, especially pp. 24-28. 

38. Quichua. See Discussion in Zerries, 1964:92, for the use of wilca (or vilca) snufif 
among the Andean Quichua, according to data given by Safford in 1916 and by O. F. 
Cook in 1915. Cooper mentions the Highland Quechua of Peru among the consumers 
of Piptadenia, and this is also fully reflected in his Map 10 in his work for the Hand- 
book (1949), where a solid black covers most of the central part of the western 
Highland. 

39. Aymara. Zerries, 1964:95, has listed the Aymara, Tiahuanaco, as yopo snuffers and 
mentions the word coro as probably =curupa = yopo. His text seems to indicate 
that the yopo powder should have been known among the Aymara through the old 
tribes in northwest Argentina. La Barre, however, does not mention yopo among 
the narcotics in his work from 1948, but he has the information from Bertonio, 
" Sincantatha: Tomar tabaco por las narizes. Thusa thusa es el tabaco" (La Barre, 
1948:66). 

Max Uhle (1898) was the first to take up a serious discussion about what kind of 
snufi really was used in the Highlands. Garcilasso de la Vega's information is clear 
and refers to tobacco: "The Indians made great use of the herb of plants which 
they call Sayri, and the Spaniards called tobacco. They applied the powder to their 
noses to clear the head" (Markham, 1869:188). According to Uhle, we learn from 
this source "that the practice of snuffing must have been nearly general in the High- 
lands of middle and southern Peru," . . . Uhle here refers only to the snuffing of 
tobacco. 

It is in one of the sources known to him, namely a report from La Paz found in 
the "Relaciones Geogrdficas de Indias, Peru," vol. II, p. 76 (Madrid, 1885) that we 



269 



Legend to Map in Figure 25 — Continued 



find the word coro. "Hay tambien entre los indios tahaco, que ellos le llaman sayre, de 
que los negros usan mucho, y los indios de la ralz que llaman coro, y se purgan con ello 
y lo toman en polvos." Uhle (1898 : 17) comments: "There is nothing published which 
points to the practice of snuffing the powder of niopo in Peru, if not in the report of 
the province of La Paz. In this province two powders were used as snuff — tobacco 
and coro. This coro, without any hesitancy, should be declared to be curupa, if it 
had not been reported as being a root. But the use of niopo being confirmed from the 
region of C6rdoba, it seems more reasonable to suppose that the writer of the report 
was mistaken than that there existed a third powder, never elsewhere reported, with 
a name similar to that of niopo, which was taken as snuff in the environs of La Paz." 

40. Desano and Tariano. Two Arawak tribes along the lower part of the Colombian 
course of the Uaupes River. According to Uscategui, 1959 : 295, they know "and 
employ paricd or Virola-simS as do their Tukanoan neighbors." Paricd (pa-ree-kd) 
is a loan-word from the Tucano but of Tupi-Guaranl origin (cf. No. 25). The tribes 
are also called Desana and Tariana. 

41. Kuiva, Amorua, Sikuani, and 

42. Guayaberos. "Various tribes," according to Uscategui, 1959:299, "located between 
the Meta and Inirida Rivers, most of which belong to the Arawak and Guahibo 
linguistic families." He has for these tribes or tribal groups received personal com- 
munications from Medcn and Schultes. Other tribes mentioned by Uscategui in this 
context are the Puinave, Piapoco, Saliva, and Kuripako, which already have been 
listed separately: 

"All of these use or were formerly acquainted with yopo, especially for purposes 
of magic. Yopo, prepared from the toasted and pulverized seeds of Piptadenia pere- 
grina, is normally taken only by men, for there exists a certain taboo which, however, 
seems no longer so strict as it cnce was. In the most acculturated of these people, 
both sexes take it. Snuffing of this violent intoxicant, which looks rather like ground 
coffee, is carried out with very different kinds of instruments, the most generally 
used of which is a double Y-shaped tube of bird bones (the arms of the Y being sol- 
dered into place with pitch) ending in two hollowed palm-nuts. These nuts are placed 
at the opening of the nostrils, and the powder is inhaled from the palm of the hand. 
Another kind is the long V-shaped snuffing tube, one leg of which is inserted into 
a nostril, the other into the mouth, thus making self-administration possible. There 
are additional types of snuffing-tubes as well, both of bone and of small bamboo-like 
grasses. One other primitive type is made of a palm-leaf: the apex of the leaf is cut 
off truncated, and this funnel-shaped end is placed over the snuff, while the snufifer 
draws in strongly through the petiole which is bound into a tube. Generally, some 
kind of wooden mortar and pestle is used to grind the Piptadenia-seeds which have 
previously been roasted in the fire. The powder is kept in a case made of the leg-bone 
of the jaguar, partly closed with wax and adorned with feathers. The addition of an 
alkaline admixture may or may not be the practice." This long quotation with its 
excellent description to which practically nothing could be added has been taken 
from Uscategui, 1959:299-300. 

43. Caripuna. A Panoan-speaking tribe referred to by the Austrian naturalist Johann 
Natterer as having snuffing implements. Natterer himself encountered a Caripuna 
subgroup, probably the Sinabo, at the Madeira River (quotation from Metraux in 
Wassen, 1965:47). According to Metraux "the Caripuna provoke a state of trance 
by taking paricd (Piptadenia sp.) in the form of clysters they administer to each 
other with rubber syringes provided with a bone tube." 

The distribution of tobacco snuffing (and. other ways of taking tobacco 
as chewing, drinking, and licking) in many cases covers the same areas (see 
map 10 in Cooper, 1949, and maps 11-12 in Zerries, 1964) . These data, how- 
ever, have not been considered here, as I have had to limit myself to special 



270 



powders.^^ The legend to the map in fig. 25 gives the available information in 
a concentrated form. 

What we learn from the map in Fig. 25 is the concentration of the use of 
psychotomimetic snuff drugs to certain regions of South America with a 
western and northw^estern dominance, if we consider still remaining tribes 
or such extinct or no longer snuffing tribes from which data have been 
recorded. What we do not learn from the map, but perhaps may recognize 
by reading the legend, is how very few good observations there are. This 
fact is deplorable, as it is obvious that we now face in the Uaupes region a 
strongly disappearing usage (cf. Wassen, 1965 : 16-17) . 

A scattered information on the use of paricd or yopo, by which words 
mostly a snuff prepared from Piptadenia seeds seems to be understood, has 
been saved. When we turn to other kinds of psychoactive drugs such as the 
snuff prepared of exudates of Virola species, the available data is sparse 
indeed. It is only through the intensive field work of such an eminent 
botanist as Richard Evans Schultes, the repeated collecting and observations 
among the Waica of Mr. George J. Seitz of Rio de Janeiro, and scientific 
research by Prof. Bo Holmstedt, that we now are able to fully grasp the 
outstanding importance of this drug. 

It is in our days mostly impossible to find out merely from vague ethno- 
graphical descriptions, which kind of snuff many tribes have been using; 
if a pure powder or a mixture, and in the latter case which ingredients. It 
was only through a chain of lucky detective work in the documented museum 
material in Gothenburg, that I was able to trace back to the Tucuna 
Indians the perfect and unusual snuff tablet No. 1219 in an 100-year old 
Brazilian museum collection in Oslo (see Fig. 26, and Wassen, 1965: 80-86 
with illustrations). It has also only been possible to consider another of 
the three snuff trays in Oslo (No. 1169) as probably Tucanoan (see Wassen, 
1965: 68-80), through an ethnographical comparative ornamental study 
in several museum collections. It is this unique specimen with its double 
human figures as handles (Fig. 27) which especially leads us to look for 
an origin in the Amazon region also for the snuff trays among the Atacameno. 
There are many tablets in the Atacaman collections with two human figures 
as handles, but I use this opportunity to refer specially to a specimen from 
Calama, Antofagasta, Chile (fig. 27) , now in the collection of the Field 
Museum of Natural History, Chicago. Dr. Carl Schuster of Woodstock, 
N.Y., who takes an extreme interest in all double-headed figures, writes 
to me (May 9, 1966) that "the fact that the two-headed snuff tray as a 
type occurs in N.W. Brazil, N.W. Argentina and Chile is very interesting. 
Double-headed human figures begin in South America archeologically 
very early — with the Valdivia Culture in Ecuador; and I know of some 
ethnological specimens (Caduveo, Mato Grosso), etc." 

As already declared, this study is not dealing with the snuffing of tobacco. 
Such a study has, however, been undertaken by Zerries in his Waika-hook 
(1964: 93-95, map 11). Naturally, this Americanist when trying to sum- 



For the rap6 dos indios from the Olmediopereiea sclerophylla tree, see Schultes, R. E. 1963 : 26. 



271 



marize the details of both distributions, had the same difficulties everyone 
must find in the sources, namely that many times we cannot differentiate the 
two kinds of snuff when reading the reports. For instance, the Guapore tribes 
are mixing yofo and tobacco powders, and many tribes use both powders. 
Zerries (1964 : 95) exemplifies the latter cases with Waica, Piro, Tupari, etc. 




Fig. 26. — Wooden snuff tray representing the prego monkey demon of the Tucuna 
Indians. Length 25 cm. Coll. and courtesy of the Oslo Univ. Ethnogr. Museum. Spec- 
imen No. 1219. 



272 




Fig. 27. — A, Wooden -paricd tray, length 20 cm. Probably Tucano. Specimen No. 1169 
in the Oslo Univ. Ethnogr. Museum. B, Snuff tray of wood, archaeological find from 
Calama, Antofagasta, Chile. Length 15 cm. Coll. Field Museum of Natural History, 
Chicago. 

The distribution of the snuff taking indicates that we have to look upon 
northern and northwestern South America as the origin area for both 
powders. Zerries also stresses this fact and points out that we, with such 
an important exception as the Maue, generally do not find the habit of 
snuffing among the Central Tupi tribes. According to Zerries (p. 95) Eastern 
Brazil should not be taken into account at all, as the only statement is 
dubious. I translate the following from Zerries work (1964 : 92) : "When Uhle 
(1898, p. 163/4), following Martyr, wants to credit the Tupi of Eastern 
Brazil for snuffing paricd, this seems unlikely.^'' He supports this state- 
ment with the information that such a specialist on the Tupi-Guaranl 
peoples as A. Metraux does not say anything about such a habit among 
them. This is perfectly correct, and as has been conclusively shown by 
Metraux in his work on the religion of the Tupinamba (1928: 88), these 
Indians were blowing smoke of the petun plant (tobacco) from a tube for 



273 



magic and healing purposes. On the other hand an examination of the 
text in Uhle's paper shows that he (dealing with the parted snuffing) uses 
the phrase ". . . and has been occasionally ascribed to the Tupis of Eastern 
Brazil." The reference given by Uhle is the small paper by A. Ernst (1889) , 
but Zerries had been misreading and found the name of Martyr on the line 
just above. The old chronicler should be omitted in this case, and Ernst 
on page 135 of his paper, to which Uhle refers, is only mentioning an Old 
Guarani word petycui which has been translated with '■'■po (powder) de 
tahaco para ser aspirado.^'' 

Leaving the Eastern Tupi aside we must, however, keep in mind that 
the very words curupd and paricd for the snuff of Piptadenia originate 
in the Tupi-Guarani languages, and were spread through the Lingua geral 
(Friederici, 1947: 229). Esteban Pinto has written in a paper on the medi- 
cine-men among the Tupinamba, that they, in order to get in a state of 
ecstacy, used '■Hlmogenicos o estupefacientes^ indicados genericamente con 
el nombre de Kurupd (Pardal)." This plant he identifies with Piptadenia 
species. As a source for the information he gives only '■''algv/nos testinwnios.''^ ^* 

With the Tupi word curupd in mind, we must realize that snuff taking 
does not always follow the language families. Zerries has found how, for 
instance, several Arawakan tribes north of the Amazon are yopa snuffers, 
while other tribes of the same language stock south of the river take tobacco 
snuff. Most probably the botanists would be the best equipped to find if 
such a varying use has its explanation in the distribution of the botanical 
species. In the following chapter, I am suggesting that the old word cohoha 
from the West Indies and a word khoba, now used in the Atacameno region, 
should be the same, and have spread south via the Arawak and the Andes. 
This finds a support in the observations by Zerries that we should ascribe the 
very habit of snuff taking to a sub-Andean stratum of tribes. Here the sub- 
Andean Arawakan tribes fit, and Zerries finds it probable that the clue 
to the snuffing should be found among the Arawak, and that the use of yopo 
should be considered as the oldest of the two main classes of snuff. 

In my work from 1965 I have treated the same prc^blems, pointing to "a 
common old tradition in the Amazonian and sub-Andean regions" ; equally, 
I have stressed the fact of "an obvious northern Arawak influence far 
south into northwestern Argentina" ( Wassen, 1965 : 77-78) . 

Comparative Outlooks and Symbolism 

Certain living and extinct tribes and certain archaeological and ethno - 
graphical objects have been mentioned in this paper in regard to their im- 
portance for the whole study. We have first the ceremonially used cemi-&gures 
of wood and stone in the West Indies, with platforms on top for the placing 
of cohoha. A mainland ethnographic equivalent to these Antillean cohoha 
"platforms" are the table tops used by the Tupari in Brazil when snuffing 
ceremonially. 

" Pinto, Esteban. 1944 : 324. 



274 



We have through Oviedo's drawing, the descriptions in words and the 
find in the La Gonave cave, a fairly good knowledge of the more simple and 
the more elaborated snuff tubes of wood on the Islands. These specimen 
have their counterparts in the Y-shaped tubes used among many mainland 
tribes. We recognize the round snuff trays, which Las Casas describes from 
the Antilles as perfectly made pieces, when we see the generally much simpler 
round trays used by the Llanos tribes of northern South America, and cer- 
tainly also the more unusual round snuff trays found archaelogically in the 
marginal Atacamefio region. For the latter I refer for instance to plate 34 
in Le Paige's description of San Pedro de Atacama (1965) , where the author 
refers to a grave for 25 adults, a child's offering and also the offering of 
snuff trays. Finally, we are certain to look for the origin of the cohoha drug 
itself in the now more and more studied species of plants which botanically 
belong to the South American mainland. But the very word cohoha! Would 
it be possible to trace it back to some actual situation and still find it used 
on the mainland? It looks as if it should be possible, and I will return to 
this problem later in this chapter. I have already mentioned that the word 
Gojoha occurs in northern Venezuela. 

In this paper I have repeated my opinion from 1965, that the elaborate 
stone figure from the R. Trombetas region shown in Fig. 13 has been espe- 
cially sculptured and used to hold a psychotomimetic snuff. The whole char- 
acter of this famous piece is ceremonial, and we meet in the sculpture a very 
important South American combination of man and jaguar. It is therefore 
a small but important piece of information that we have from Dr. Schultes, 
when he tells us that the Inga and Kamsa Indians in the Valley of Sibundoy, 
Colombia, called a narcotic prepared from the leaves of Methysticodendron 
Amesianwni, mits-hway horrachero, or the "intoxicant of the jaguar." Even 
if no further explanation has been given as to the nature of the relationship 
jaguar — intoxicant — ^we have at least an indication of a connection between 
the feline and an intoxicant with certain properties for the users. May we 
guess that the jaguar is thought of as the "owner" of the drug? 

The alter-ego sculpture in Fig. 13 is of stone. When we try to get a picture 
of the archaelogical distribution of snuflang paraphernalia in the Amazon 
region, we must take into account that very little of perishable material, such 
as wood, has been saved to our days. As pointed out in Wassen, 1965 : 77, an 
origin in the Highland Tiahuanaco has often been considered for the trays 
and other snuffing paraphernalia now found in northern Chile and north- 
western Argentina. Apart from the fact that snuffing paraphernalia now 
have been dated in Chile to an earlier epoch than that with an influence from 
Tiahuanaco, I have for ethnographical reasons considered an origin of the 
marginal Atacameno snuffing material in the Amazonian and sub-Andean 
region. I have later found that Rene Naville, in an article published in 
Switzerland in 1959, more or less has been of the same opinion ; that is, that 
we should look for the origin of the snuff ceremonialism in the Amazon re- 
gion, possibly among the Arawak Indians; but that later a cult associated 

65 Schultes, R. C. 1955 : 10. 



275 



with it in the Atacama region and manifested in human offering, had an 
Andean origin. Mr. Naville's contribution to the whole problem is valuable, 
and I prefer to quote him here in his language, French : 

On peut conclure en disant que si I'absorption d'un narcotique au moyen de tubes et de 
tablettes semble etre originaire d'Amazonie, peut-etre arawak, son usage rituel et son 
association avec le culte rendu a une divinite accompagne de sacrifices humains est 
tres probablement d'origine andine. II est done possible que ses deux pratiques se soient 
conjointes dans le Nord du Cbili et le Nord-Ouest de 1' Argentine, points d'intersections 
des grands courants culturels venus du Nord et de I'Est, pour donner naissanee aux 
pifeces decrites plus haut.™ 

From what already has been stated in this work, it is with full evidence 
clear that wooden tablets and tubes for the taking of some kind of a snuff 
must have been of outstanding importance in the now marginal region where 
once the Atacameno dominated. According to Bennett ( 1946 : 599) , "the term 
Atacameno {Atacama, Kunza) refers to a people, with a distinctive language 
and culture, who once occupied the northern Chilean provinces of Tacna, 
Arica, Tarapaca, Antofagasta, and Atacama, and much of the Northwest 
Argentine provinces of Los Andes, Salta, and Jujuy." "Today, the few re- 
maining Atacameno are located in isolated sections of Chile and the Puna de 
Jujuy, but culturally and linguistically they have been absorbed by Ayrroara 
or Spanish." 

One may ask if in such a region anything is remembered about the ancient 
me of snwffing paraphernalia among the modem mestizo population? 

As the Atacameno were basically agriculturists and herders, my question 
came after I had read two special articles both dealing with the actual culture 
of typical parts of the old region.^"^ Both authors, Horst Nachtigall (1965) 
and Ana Maria Mariscotti (1966) underline the importance of traditionally 
old offering ceremonies to Pachamama, so-called senaladas, during which 
the offers of llama animals (or part of them) , alcohol, chicha, coca leaves, etc. 
are obligatory and important. 

The cultural correspondence with the samiri concept among the Aymara 
and Chipaya Indians of the Highland as studied by the late Alfred Metraux 
during his expedition in 1930 seems important for a very special reason, 
namely that it has been suggested by Sven Loven that we consider the Taino 
word cemi as related to Samiri, because of certain facts, among them that 
the Arawak had asserted themselves also in the western Highland.^® 

On my written question to authors Nachtigall and Mariscotti both declare 
that the former use of the tabletas de rape, tubes, etc. now is absolutely un- 
known to anybody in the actual rural population.^® 

K> Naville, Ren6. 1959 : 3. 

5' Nachtigall, Horst. 1965. Mariscotti, Ana Maria. 1966. 

^ Wass^n, H. 1934 : 633. "Dr. Sven Lov4n, at the museum of Gothenburg, has mentioned for me 
that he for certain reasons — among these the fact that the Arawaks have asserted themselves also 
in the western highland — considers the constituent sami of the word samiri to be the same as the 
Tainan zeml." 

™ Mrs. Mariscotti, after four different periods of investigation in the Quebrada de Huamahuaca 
and Puna de Jujuy can assure "that the use of the tabletas de rap6 which with such frequency 
are embodied in the "Puna Complex" of Bennett, is absolutely unljnown." (Letter, November 16, 
1966). 



276 



If we now return to the senaladas^ both Nachtigall (1965 : 216) and Mari- 
scotti (1966 : 74) report the 'burning of leaves of khoa or khoha, an aromatic 
plant for which they botanically refer to Mentha pulegnmv (of the Family 
Labiatae). This is said by La Barre to be used also amongst the Highland 
Aymara.'"' With a letter of December 5th, 1966, Mrs. Ana M. Mariscotti has 
had the kindness to send me a botanical sample of khoha collected during her 
latest trip to Puna de Jujuy. This botanical sample has been examined by 
the botanist, Dr. Bo Peterson, chief of the Museum of the Gothenburg 
University's Botanical Institution. According to Dr. Peterson it is not at 
all the question of a genus of the Labiatae Family, but instead a genus of 
the Family Gompositae, namely Lepidophyllum quadrangulare. Reference 
has been given to Angel Lulio Cabrera's '"''Sinopsm del genero Lepidophyllura 
{C ompositaey in the Boletm de la Sociedad Argentina de Botanica (vol. 
I: 48-58, La Plata, 1945), where the author also gives the popular names 
chacha and coba for this plant. 

In accordance with what has been said above regarding a possible rela- 
tion between the word samiri and the Island Arawak cem^, it is also inter- 
esting to suggest a relationship between the Island Arawak (Taino) word 
Gohoba and the khoba for an aromatic herb in the former Aracameho region 
with its influence from the Highland and its trade relations. I would like 
to suggest that cohoba and khoba are the same words, even if they now refer 
to different plant material and are used in two widely separated geographic 
areas. The word we still meet so far south in the form khoba should in that 
case belong to an old stratum of Arawak influence. Professor Nils M. Holmer, 
specialist on Amerindian languages, write to me (November 17, 1966) that 
he is sure that an Andean khowa {khoa) with a strongly aspirated kh-^ may 
have been heard as cohoba. 

The senaladas among the present rural mestizo population in Puna de 
Atacama and Pune de Jujuy represent offshoots of an old Highland tra- 
dition with offering to a deity (Pachamama) principally ruling the agricul- 
tural cycle. To the Indians, gods, or spirits, were benevolent or ill-disposed, 
and the medicine-men or other important tribal functionaries had to face 
a situation which I described in 1965 as influencing the benevolent ones and 
to weaken or if possible destroy the ill-disposed ones. I have also said that 
"we are in our full rig'ht to believe that such important goals have been 
reflected also in the art of the Indians, even if we now mostly lack the 
mythological or other information explaining the connections" (Wassen, 
1965 : 38) . As the psychotomimetic snuffs must be considered as a means of 
contact with the spirit world, it is consequently fully understandable that 
we find Indian representations of their supernatural beings expressed in the 
art concerning the snuffing paraphernalia. We can, as an example, mention 
the ja-guar motif in the sculpture on ethnographically known snuff trays 
from the Cashuena Indians of the Trombetas and Cachorro Rivers, Brazil.*'^ 

*° La Barre, Weston, 1948 : 184. "The leaves and stems of qoa (Mentha pulegium Linnaeus) are 
burned in the fields "to malce a good harvest," but it is uncertain if this is done for magical reasons, 
or for the same sound fertilizing reasons with which they place animal manueres on the field." 
Cf. same author, p. 56, about the use of Mentha pulegium, as a condiment. 

" See Frikel, 1961, describing the moH feast. Quoted in Wass6n and Holmstedt, 1963 : 21-23. 

277 



As the illustration on page 8 in Frikel's paper of 1961 on the nwri feast 
among the Cachuena unfortunately is very unsharp, I am glad that, thanks 
to my friend Dr. Carl Schuster of Woodstock, N.Y., I can publish two 
photos here (Figs. 28 and 29) of the Cashuena specimens. Fig. 28 corre- 
sponds to the illustration on page 8 in Frikel's paper. Among the implement 
for snufSng mori^ the "shovel" or tray at the right has two confronted 
jaguars on its haaidle. Frikel calls the snuff tray yard-kukuru^ which in 
Cashuena means "figure of the mythological onga (jaguar) yara^\ The 
yara are '■'■hichos do fvm,do, da agua^'' "water- jaguars", conceived as a pair, 
male and female,''^ a fact also of interest for the principle found in Amazonas 
that "magical substances are always in pairs, male and female" as discussed 
in Wassen 1965 (p. 76) in regard to the double-headed paricd tray of Tu- 
canoan origin. The Cashuena used to have special songs, iwarawd-yorenmru^ 

62 Frikel. 1961 : 7-8. 




Fig. 28. — Cashuena Indian snuffing paraphernalia for t,he morl feast. Mythological 
'water-jaguars' form the handle of the tray. Photo courtesy Dr. Carl Schuster, Wood- 
stock, N.Y. Collection in Brazil. 



278 



Fig. 29. — Pair of jaguars, one, as of 1954, "three or four generations old" handle of a 
Cashuena snuff tray. Coll. in Brazil. Photo courtesy Dr. Carl Schuster. 

for their snuffing boards. It is deeply regretted that they now are lost (Frikel, 
1961: 9) as they probably could have helped to explain the symbolism of 
the carved motives. As regards the Maue we have the statement by Pereira 
(1954: 68) that their medicine-men {pages) used the paricd to get in trance 
and be able to contact their gods of the waters and the jungle. We are 
probably save to assume that the "water-jaguars" of the Cashuena stand 
for such deities or spirits. 

Dr. Carl Schuster took his photo in Fig. 28 in the Convento dos Francis- 
canos in Santarem, and the objects were then said to be kept in a Franciscan 
museum at Ipauarana, Paraiba State. At the same time (November 1954) 
Schuster also copied a photo of an handle of aji old snuff tray from the 
Cashuena, said to be 3 or 4 generations old, c. 80-100 years. This handle 
(Fig. 29) has been published in a drawing on page 7 in Frikel's paper from 
1961. We see a pair of jaguars, originally with beads in their eyes. Father 
Frikel informed Dr. Schuster at the time, that a complete tray which he 
wanted was buried with a shaman. This information confirms my statement 
from 1965 : "If also in former days the carved and ceremonially used snuff 
trays were placed with the dead this could very well explain their scarcity 
in collections.^^ 

For the tribes of the Uaupes-Caqueta region, Groldman has informed us 
that "the shaman in the area is generally referred to as a jaguar, and com- 
bines the functions of medicine-man and sorcerer. Older shamans assume 
the guise of the jaguar and are particularly feared. Every jaguar who at- 
tacks human beings is assumed to be a shaman, and a shaman who is sup- 
pected of such an attack is not infrequently put to death. As the spirit of a 
murdered shaman enters another jaguar, however, little relief is expected 
from killing them" (Goldman, 1948: 796). Bodiger (1965: 150) has shown 
how the names for jaguar and shaman are similar or identical in many of the 
tribal languages, and how the shaman through this identity in name is con- 
sidered to have the power of transforming himself into a jaguar — this in a 
detailed investigation of the Tucano religion. 

Again and again we come back to the importance of the jaguar motif 
for paraphernalia related to snuffing. It is most likely that tribes using 
jaguar leg-bones as snuff containers do this out of some magical reasons 
related to the real and magical power of the animal. And, when we find a 

" Wass^n. 1965 : 74. 



279 



4 cm. long puma, figure of stone dominating the snuff tray No. 10718 from 
Tiahuanaco in the Ethnographical Museum of Buenos Aires (Coll. De- 
benedetti, 1911), it is really not surprising (Fig. 30).*^ In the tabletas de 
rape of the Atacameno, the jaguar is seen as a mighty god. Also for this a 
highly interesting parallel with pure Amazonian ethnographical material 
can be presented. 

In the Ethnographical Museum at Munich we find the so-called Erlangen 
ceremonial staff, an object wMch has been studied by Zerries and by him 
found to be a medicine-man's staff, probably from the Carib Warikyana 
or Arikiena of the Kachuru (Cachorro) River. Frikel considers the 
Cashuena, often mentioned in this work, as descendants of the old Warikyana 
(see Wassen, 1965 : 33), and consequently every old piece of art from that 
tribe or region must to be of immediate interest also for a study of cere- 
monially used snuff trays. Zerries found on the Erlangen staff the super- 
natural vulture, the medicine-man's most important helper, and the figure 
of a jaguar, "the werwolf of the South American shamans."^ An ajithro- 
pomorphic jaguar (or "werwolf" figures) is now seen in Fig. 31 from photos 

Photo kindly supplied by Dr. Carl Schuster. 
"5 See complete description in Zerries, 1962, and his photo on p. 615. 




Fig. 30. — Snuff tray with 4 cm. long puma of stone. Tiahuanaco. Coll. No. 10718 (De- 
benedetti, 1911), Museo Etnogrdfico, Buenos Aires. Photo courtesy Dr. Carl Schuster. 



280 



Fig. 31. — Ornamental detail, anthropomorphic jaguar on a trumpet of hard red wood. 
Old specimen in the Pitts Rivers Museum (No. 130, J. 44), without provenience but 
certainly from the Lower Amazon Region, probably the old Warlkyana. Photographs 
courtesy of Mr. Jeremy P. S. Montagu, London. 

which have been kindly supplied by Mr. Jeremy P. S. Montagu, London. 
The figure shows a "side-blast trumpet made of two semicylindrical pieces 
of hard red wood." This specimen, now in the Pitt Rivers Museum (entry 
130.J.44) came from "the Bodleian" to the University Museum in Oxford, 
presumably, then transferred to the Pitt Rivers Museum in 1886." It is 
an old piece of Indian art for which the provenience is lacking, but as far 
as I imderstand it should be referred to the same region as the Erlangen 
staff, that is, the Lower Amazon region and from the old Warikyana in the 
art center of the Rio das contas (cf . Wassen, 1965 : 34) . A similar 123 cm. long- 
trumpet with jaguar motif (his tail curled down) from an old collection 



262-016 0-67— 20 



281 



Fig. 32.— Snufif tray from "Quitor 5", San Pedro de Atacama, Chile. Dominating an- 
thropomorphic feline god. Drawing after photographic illustration in Le Paige, 1964. 

and the Amazon is found in the Rijksmuseum voor Volkenkunde, Ley den. 
It belonged originally to "Het Kon. Kabinet van Zeldzaamheden." 

An important detail in this jaguar-man on a trumpet is the tail, which 
goes up on the back and ends in a characteristic curl. The reason I find it 
important might be understood from Fig. 32, in which the figure on a snuff 
tray found in "Quitor 5" in the region of San Pedro de Atacama, Chile, by 
Gustavo Le Paige, has been copied from plate 125 in Le Paige's work of 1964. 
The snuff tray from Chile is an expression of the same idea of a jaguar (or 
puma) -man-deity as found on the old trumpet, and the tail is a characteristic 
of both figures. To me these specimens form another link in a chain of evi- 
dence for an early Amazon cultural influence on the Atacaman region. 
Thanks to a numerous series of snuff tray finds in the dry region. Father Le 
Paige has been able to demonstrate specific manifestations of magico-reli- 
gious art in which the taking of a man's head is involved. In snuffing para- 
phernalia which he found, he can follow a complete series of ceremonies, from 
the presentation of a condemned man with backbound hands and the execu- 
tioner with his attribute, an axe, to the priest carrying the head of the vic- 
tim — in that important moment imitating the sacred puma god by walking on 
all fours and carrying a puma mask and the wings of a condor.*'' 

°« Le Paige, Gustavo. 1964: 61. Mostny (1964) has been able to show such ceremonialism also 
in the petroglyphs of Angostura, Prov. of Antofagasta, Chile. 



282 



Gustavo Le Paige and other archaeologists working in the Atacaman re- 
gion find this richness of evidence thanks to a dry climate. What the anthro- 
pologists have found, or may expect to find, in the eternally wet Amazon 
region, are just a few fragments of a formerly rich ceremonialism in which 
the taking of psychotomimetic drugs seems to have been integrated. 

A group of snuff trays from the Amazon region with an obviously im- 
portant zoomorphic motif are the Maue specimens said to depict caymans or 
snakes. Several of these old fine Maue wooden trays have fortunately been 
saved in museum collections.^^ The specimen in Oslo is shown also here (Fig. 
33) . Typical for most of the Maue trays, is the fact that they are rectangular 
in form and have a finely polished depository for the snuff, open on the edge 
of the board. The other edge of the tray ends in an animal's head, often 
with an accentuated tongue, a trait typical for representations of snakes but 
hardly for caymans in which the tongue is not easily observable. It is true 
that a Maue Indian has once stated that a paricd tray owned by him repre- 
sented a yacare, but as I have said, this label can not be stamped on all snuff 
trays from this tribe.''^ Anthropological colleagues such as Etta Becker-Don- 
ner in Vienna, and Antonio Serrano in Argentina, as well as Otto Zerries in 
Munich, seem to favor the idea of snakes."^ The Atacama specimen published 
in Fig. 22 has, however, a feline head. As this archaeological specimen is 
much older than the 19th century ethnographical objects from the Maue, it 
is of interest also for the discussion of the Maue pieces. As a matter of fact, 
some of the Maue tray handles in the form of animal heads may be con- 
ceived as conventionalized feline heads, perhaps with some idea of "water- 
jaguars" behind as in the case with the Cashuena. The outstreatched tongue 
is accentuated in the feline powder cup published as Fig. 5 in Zerries : 1965. 
A most interesting snuff tray with two feline heads found in a grave at the 
Pucara de Lasana (Rio Loa, Chile) has been published by Spahni (1964, 
Fig. 5). His Fig. 4, showing a snuff tray from another grave said to repre- 
sent an armadillo, most probably also depicts a feline. 

Another group of animals which in a particular symbolic and magic way 
seem to be connected with the use of drugs are birds with very good eyesight, 
such as eagles, vultures, very often condors, and also such good night -hunting 
birds as owls (the Cashuena snuff tray in Fig. 28) . I have treated this in 
detail in my work from 1965 (pp. 24-29), and I can reiterate here, that we 
are entitled to consider birds as patrons for ecstatic intoxication in several 
Indian societies. I refer, for instance, to snuff trays with condors, bird-shaped 
snuffers, snuffing tubes which terminate in hollow nuts, often shaped like 
a bird's head (Fig. 34), and also, to direct explanations by medicine-men 
that they use feather crowns, etc. so that they may see better into the world 
of spirits. This connection between the shamans as users of drugs and the 
world of bird-spirits is a fact. The reason for it is probably to be found in 

«7 See figs. 8, 10, 11, 12 and 15 in Wass6n 1965. 

«8 Wass6n. 1965 : 43. 

89 Wass6n. 1965 : 43 and 50. 



283 



Fig. 34. — Snuff tubes from the Guapore Territory. A, Monde Indians, after photo by 
Caspar; B, Salamay Indians, coll. Mus. f. Volkerkunde der Univ., Zurich, No. 11307; 
C-D, Tupari Indians, coll. Dr. Franz Caspar in the Mus. f. Volkerkunde, Basel, No. 
IV C 9052, length 88 cm. (photo and drawing of the same tube). 



285 



the drugs/" and I point, in passing, to the complex of Siberian shamans being 
described as of bird-type, who visit the spirits up in the air. This, inci- 
dentally, is a contrast to the other type of Siberian shamans, who have their 
contacts in the world belowJ^ The ideas among the Koryak about the Big- 
Raven and the fly-agaric give a good illustration of this.''^ I hope that later 
a common component will be found in all this, through the analytical work 
by experts on the drugs involved. 

No specific search has been performed for this paper regarding the pos- 
sible use of snuff tubes outside America, where they seem to be autoch- 
thonous." Br. Gordon Willey (1966: 22), has counted "the chewing of lime 
or ashes with some kind of a narcotic" as one of the very ancient traits, pos- 
sibly the survival of a Palaeolithic heritage, which "are shared by Asia and 
the New World." Willey naturally refers to the use of betel-nut in Asia and 
the coca leaf in South America, and he finds a considerable age for the trait 
in the Americas. 

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289 



The Botanical Origins of 
South American Snuffs 

Richard Evans Schultes 

Botanical Museum of Harvard University, Cambridge, Massachusetts 

Page 



I. Introduction 291 

II. Princii)al Sources of South American Snuffs 292 

III. Sources of Snuffs of Lesser Importance 302 

IV. Final Query 304 

V. Bibliography 305 



Introduction 

Man in primitive societies the world around has found the most ingenious 
Avays of administering narcotics. Intoxicating plants, or products from them, 
have been chewed in crude form or variously elaborated and consumed. They 
have been drunk as decoctions or infusions. A few have been prepared in the 
form of thick syrups or pastes that are licked or smeared on the tongue or 
gums. Some have been smoked directly, as in pipes, cigars or cigarettes, or 
the fumes of them have been inhaled in sundry ways. There are those that 
have been applied to the skin or membranes in the form of ointments or 
unguents. Several are known to have been taken as an enema. Snuffing has 
been the preferred method of using a niunber of these agents. 

The verb to snuff (and the corresponding German schupfen and Skandina- 
vian srmsa) , stems, of course, from the same Germanic root that has given us 
the English word to sniff. There is a significant difference between the two 
actions. Whereas one sniffs an odour or fragrance — that is, a substance such 
as an essential oil, smoke or ethereal component of the atmosphere — one snuffs 
actually solid substances variously inserted or drawn into the nostrils. 

The snuffing of plant materials for narcotic, especially for hallucinogenic, 
effects seems to be peculiarly New World. To be sure, sternutation induced 
by various means is a recognized therapeutic practice in many cultures. In 
the Middle Ages, European medicine recommended sternutation to draw 
off bad humours. Hellebore, the German Niesicurz and English sneezewort, 
was one of the most favoured therapeutic sternutatory powders taken into 
the nostrils together with marjoram and other plants to cleanse the brain 
through sneezing. Sternutation was used even for prophesying and in super- 
stition and magic. A person who sneezed on New Year's morning, for example, 
would not die during the year. Snuffing now refers usually to the use of to- 
bacco. This is true in languages other than English. The German schupfen, 
for example, has been more or less restricted to the snuffing of tobacco and 
other stimulants since the 17th Century. 



291 



It does seem probable, however, that the use of narcotics as snuffs is of 
American origin and that it went to the Old World with tobacco. The custom 
of snuffing tobacco, widespread apparently in pre-Conquest America, became 
common and accepted as a recreational practice devoid of therapeutic intent 
in Spain during the first quarter of the l7th Century. There is evidence that 
it was imported directly from the New World and that tobacco snuffing, 
as well as chewiag and smoking, represents one of the most significant cul- 
ture traits passed on to the western civilisation from the American aborigines. 

Principal Sources of South American Snuffs 

Undoubtedly the most important snuffing material in pre-Conquest Amer- 
ica was tobacco. At least two species of tobacco, possibly several additional 
ones, are known to have been employed as a narcotic {4-) . These two are Nico- 
tiana Tdbacum and N. rustica. Nicotiana Tabacum, from which comes most of 
the tobacco that is smoked, snuffed and chewed at the present time, was like- 
wise the source of most of the narcotic in pre-Conquest South America, Middle 
America and the West Indies. Originally a tropical species, it has been 
cultivated so long that it is not known in the truly wild state. Nicotiana rus- 
tica^ native to North America, where it is still wild in some localities, is a 
hardier species thought to have originated in Mexico. It is this species that 
was smoked and probably snuffed by Indians of Mexico and North America 
before the arrival of the European. Europeans introduced Nicotiana Tdbacum 
from the Old World to North America long after the Conquest, and imtil 
this introduction, it was apparently unknown in most of the territory now 
included in the United States and Canada {9) . 

Although there are indirect evidences that tobacco may have been taken 
as snuff in Mexico and other parts of North America, there can be no doubt 
that in much of South America this was the most widespread method of 
utilizing the narcotic, especially in the wet, tropical lowland areas, such as 
the Amazon Valley. So nfany observations attest to this fact that there would 
seem to be little if any need for a discussion of the custom, were it not that 
perhaps confusion as to the source of a number of snuff preparations may 
have led to the assumption that tobacco snuffing, though widespread, might 
have been even more widespread than it actually was. Yet botanists and 
anthropologists have consistently warned against such generalisations. Mason, 
for example, stated {13) that "the snuff taken throughout . . . most of the 
Amazon and West Indies ... is more frequently made from other plants 
than toibacco." And Cooper owned (^) that "tdbacco snuffing . . ." is "not 
always distinguishable in our sources from Piptadenia snuffing." 

Garcilaso de la Vega {8) reported that the Inca did not cultivate tobacco 
or sayri, but they are thought to have utilised several varieties native to 
the Andes, the roots of which were pulverised and used medicinally and as 
a snuff {To) . 

Botanists are understandably wont to be somewhat more conservative 
in ethnobotanical generalisations than are anthropologists. Goodspeed, for 



292 



example, in his classic work (9) on the genus Nicotiana, wrote that "pre- 
sumably N. tabacttm was in pre-Columbian use, doubtless often in cultiva- 
tion, in the West Indies, much of Mexico, Central America, Colombia, 
Venezuela, the Guianas and Brazil. Spinden . . . apparently would extend 
this range to Peru, Boliva, Chile and Argentina, since tubes 'for taking 
snuff, presumably of tobacco, occur far and Avide* in those areas .... 
There is, however, considerable doubt that the material snuffed in the tubes 
so familiar in remains of certain ancient civilisations in the Americas was 
'tobacco' obtained either from early races of N. tabacum or from progenitors 
of the species of Nicotiana which today are native in the regions concerned. 
In other words, there is little evidence that N. Tabacum was in pre-Colum- 
bian use in western North America or in lower South America." 

Tobacco in snuffing — whether the source of the snuff be Nicotiana Tabacum 
or some other species of the genus — seems quite generally to have been 
used alone, although there are occasional reports that it is sometimes mixed 
with Anadenanthera. Amongst the tribes of the Guapore Eiver in Amazonian 
Brazil, tobacco snuff was mixed with "crushed angico leaves [angico refers 
to leguminous trees, especially to Anadenantheral and ashes of a certain 
bark" (12). During my years of field work amongst the Indians of the 
northwestern Amazon, I witnessed the preparation of tobacco snuff on many 
occasions and actually employed the snuff myself instead of smoking. The 
species used was Nicotiana Tabacum, and with two exceptions, I never saw 
the admixture of any other plant to the snuff — ^that is, other than ashes. 
These two exceptions were with the Witotos of the Rio Igaraparana and the 
Yukunas of the Rio Miritiparana of Colombia, where powdered coca {Ery- 
throxylon Coca) is added to the tobacco. It is my belief that the ashes (usually 
from bark of TJieobromxi or leaves of Cecropia) serve mainly or wholly a 
physical function to help keep the finely pulverised and sifted tobacco 
particle from absorbing humidity from the excessively wet atmosphere and 
lumping so that the material could not be used as a snuff. 

South America boasts a wide variety of containers and implements for 
the administration and self -administration of snuffs. Since there is normally, 
I believe, no relationship between these paraphernalia and the botanical 
source of the snuffs, I need not here discuss this intricate topic which 
has already been thoroughly investigated by a more competent specialist {27) . 

A critical survey of tobacco snuffing in South America, incorporating 
all of the extensive literature interpreted against the background of inten- 
sive field observations, is overdue. I venture to predict that, as such a study 
unravels the enigmas, we shall see other narcotic snuffs assume greater 
roles and tobacco find a progresively less important role than it has been 
given in our ethnobotanical evaluation. 

One of the most interesting and enigmatic snuffs of South America 
is yopo or niopo, prepared from the beans of the leguminous tree Anaden- 
anthera peregrina. During its botanical history, this plant has been placed 
in the related genera Acacia and Mimosa. It is perhaps best known under 
the binomial Piptadenia peregrina, but recent studies have indicated that 
it is most appropriately accommodated within Anadenanthera (1 ) . 



293 



Fig. 1. — Use of the straight bird-bone snuffing-tube for administration of the tobbaco- 
coca snuff of the Yukuna Indians, Rio Miritiparand, Amazonas, Colombia. Photograph 
by R. E. Schultes. 

Of possible significance is the curious fact that Anadenanthera peregrina 
is or has been employed not only in northern South America but probably 
in the Antilles as well. Tobacco snuffing was a well established custom in 
the "West Indian islands long 'before the arrival of Europeans, and the 
snuffing in Hispaniola of a narcotic, vision-producing powder called cohoba 
was no cause for intellectual curiosity, since most early writers assumed that 
cohoba was merely another tobacco snuff. It was the American enthno- 
botanist Safford who first identified, quite correctly, I believe, the West 
Indian cohoba snuff with the yopo of the Orinoco basin of Venezuela and 
Colombia {16) . 

There were a number of reports in the literature ascribing the sources 



294 



of Amazonian snuffs to various leguminous trees, and its was Bentham who 
"came to the conclusion that all South American trees . . . referred to as 
the source of narcotic snuff were probably one species and were identical 
with Linnaeus' Mimosa peregrina, which Avas first described in 1737 from a 
seedling growing in the celebrated Clifford Garden in Holland" {16). It 
seems that one of the most extraordinarily mistaken generalisations in 
etlmobotany — that all of the narcotic snuffs of the Amazon that were not 
obviously tobacco must have been prepared from Anadenanthera peregrina — 
has stemmed from Benthem's conclusions. This generalisation, of course, 
has not been without influence, judging from the state of confusion and 
lack of clarity encountered in many of the earliest reports of "smoking" 
and "snuffing." We have no clear distinction, in many early instances, as 
to whether tobacco or cohoba represented the plant the use of which was 
being described, since tobacco was snuffed in the Caribbean area at the 
time of the arrival of the Spaniards. 




Fig. 2. — Tanimuka Indian administering tobacco-coca snuff with the V-shaped bird-bone 
snuffing tube employed for self -administration. Rfo Miritiparand, Amazonas, Colombia. 
Photograph by R. E. Schultes. 



295 



Fig. 3.— Yukuna Indian pouring out into the hand from a snail-shell case a quantity of 
tobacco-coca snuff for insertion into the bird-bone snuffing tube. Rio Miritiparana, 
Amazonas, Colombia. Photograph by R. E. Schultes. 

A recently published map {4), sliowng the distribution of snuffs made 
from Anadenanthera^ includes the entire Orinoco basin and adjacent areas 
of southern Venezuela to the east; westward across the northern Colombian 
Andes, much of the Magdalena Valley ; down the Andes through Columbia, 
Ecuador, Peru and Bolivia; the coastal region of Peru, and scattered iso- 
lated areas in northern Argentina, and the central and western Amazon 
Valley. One must remember that this map refers not to one species but to 
a genus — and there have been suggestions that species other than Anaden- 
anthera peregrina have entered the South American snuff making picture. 
Furthermore, one must recall that Cooper himself cautioned that "our 
tribal records on which the . . . distribution map ... is based are prob- 
ably very incomplete. On the other hand, some of the attributions may not 
be correct, since in some cases the lack of exact botanical identification makes 



296 



it doubtful whether we have to do with Piptadenia snuff, tobacco snuff or 
snuff from some other plant . . . ." 

When I first went to the northwesternmost Amazon in Colombia — a region 
the flora of which I investigated in the field from 1941 to 1953—1 fully ex- 
pected to meet with the use of yopo snuff. One of my reasons for choosing 
this geographcal area for my studies was our knowledge that here the 
aborigines were reported to be using more kinds of narcotic preparations 
than in any comparable region of the world. Consultation with the sparse 
literature for this part of the Amazon basin led me to believe that yopo snuff 
from Anadenanthera peregrina was known and employed throughout the 
area. True, amongst the Witotos, Kubeos, Yukunas, Tanimukas, Tukanos, 
Makunas and other native groups, I met with the use, oftentimes excessive 
use, of tobacco snuff. I never met with anything called yopo or niopo, and 
what was more confusing to me as a botanist was my failure to encounter, 
wild or cultivated, a single tree of Anadenanthera peregrina. This species 
grows cultivated in the Llanos of Colombia — the Orinoco drainage area of 
Colombia, northerly adjacent to its Amazon area. Furthermore, from the 
writings of Spruce (^^) and other earlier travellers, as well as from reports 
of missionaries of the present day, we know that this hallucinating snuff was 
and is employed extensively and in large amounts by the naitves of the Llanos. 
My later explorations and researches in the Colombian Amazon convinced me 
that generalisation from reports in the available literature had led to gross 
error; that, in effect, yopo snuff not only is not used but is actually unknown, 
and that the tree does not occur, at least in the northwesternmost Amazon. 
Furthermore, since I was resident for three years in country of the Tikuna 
Indians of the uppermost Amazon Eiver at the point where Brazil, Colombia 
and Peru join, I was especially interested in the assmnption that these natives 
formerly made snuff from Anadenanthera (3) . Inasmuch as I met no tree 
of this species in the area nor did I see the Tikunas (who do make tobacco 
snuff) prepare snuff from leguminous seeds, I must conclude that this 
specific instance is also one of the numerous erroneous generalisations. 

How can we assume, or justify an assumption, that natives over such 
a vast area as the Amazon make a snuff from a plant that they do not know, 
that does not grow in their region, wild or cultivated, the seeds of which they 
would have to import for many, in some cases, for several thousand miles ? 

Let us contemplate what is known of the distribution of Anadenanthera 
peregrina. Safford, who apparently concurred with the ideas that such widely 
scattered Amazonian peoples as the Omaguas of Amazonian Peru and the 
Murus of the Rio Negro of Brazil prepared snuff from this leguminous tree, 
truthfully wrote that Anadenanthera peregrina "has a most appropriate 
specific name, for it has a wide geographical range." He further pointed out 
that its range had "undoubtedly been increased by human agency." But, when 
Safford cites for Anadenanthera peregrina a range comprising Hispaniola 
and Puerto Rico, Venezuela, northeastern Peru, southern Peru, Argentina, 
Guiana and "many parts" of Brazil, he was including with Anadenanthera 
peregrina two other species of the genus which he presumed to be employed 
as the source of making snuff. He cites no herbarium voucher specimens, 

297 

262-016 0-67— 21 




Fig. 4. — Anadenanthera peregrina (Piptadenia peregrina) . 



instead giving references to the use of snuffs in the literature and assuming 
that they did refer actually to snuffs from Anadenanthera. 

Fortunately, we have several botanical studies of monographic nature 
that shed light on the distribution of Anadenanthera peregrina. It is these 
data, not "interpreted" literature reports, that must guide any definitive 
generalisations. Ducke, renowned Brazilian botanist who spent more than 
half a century studying the Amazon flora in field and laboratory, specialised 
in the Leguminosae. In his "Leguminosas da Amazonia", he (5) cites all 
known collections of Anadenanthera peregrma (under Piptadenia pere- 
grina) . If the species had been much commoner in the Amazon, Ducke would 
have made more collections than those that he cited. More recently, Altschul, 
in her studies of the genus of the yopo snuff (i, £6) , has treated Anadenan- 
thera monographically, citing only collections, wild or cultivated, from South 
America. Thus, we know that, at least in the present century, Anadenanthera 
peregrina is far from common in the Amazon basin. 

It is, therefore, somewhat exaggerated to expect us to conclude that many 
tribes are preparing an important hallucinogenic snuff, and a product often 
taken in excessive amounts, from a tree that is uncommon or even not found 
in their environment. Trees of this species are reported in Venezuela as "being 
forest dominants, belonging to secondary forests, inhibiting savannas, light 
forests and riversides," in British Guiana confined to "savannas and riverside 
forests," while in Brazil represented mostly in the campos or savamias {1,6). 
The distribution of Anadenanthera peregrina in the Amazonas of Brazil is, 
significantly, confined to savanna-like areas, usually in or near the lower Eio 
Madeira and the Rio Branco basins — significantly, I say, because the Maue 
and other tribes of the Madeira area have, probably correctly, been reported 
as using snuff from Anadenanthera. I have seen excellent specimens of Ana- 
denoMhera peregrina recently collected by Mr. Georg Seitz along the Rio 
Negro, in the vicinity of the mouth of the Rio Branco, in Amazonian Brazil ; 
these were undoubtedly cultivated from material brought in from the sa- 
vannas of the Rio Branco. 

Now, let us contemplate the problems that arise. If Anadenanthera pere- 
grine is not the source of a snuff employed over wide areas in the Amazon, 
what are the sources of the numerous snuff preparations that we know are 
or have been prepared in isolated localities from the mountains of Venezuela 
and the Guianas south to the Argentine and from the eastern slopes of the 
Andes to the Atlantic Ocean? We cannot fully answer this query at the 
present time, but we can offer several tentative approaches towards a solution. 

To begin with, it is very probable that several, if not many, different plants 
formed the basis for the snuffs employed similarly and for similar purposes 
over such a vast area. We know very definitely that this is true. We do not, 
to be sure, know all of the plants involved in this complicated enigma, but 
we know enough to arrive at an overall picture to guide future research. 

It was apparently Safford {16) who first suggested that species of Anaden- 
anthera other than peregrina may be the source of narcotic snuffs in South 
America. He identified the vilca or huUca of southern Peru and Bolivia, and 



299 



tlie cebil of northern Argentina, with seeds of what he called PipUidenia 
macrocarpa, now correctly referred to as Anadenanthera colubrina var. 
Cebil. Although the evidence is, in my opinion, rather weak, several other 
species and varieties may have been employed in isolated localities in south- 
em South America. Inasmuch, however, as a paper in the series is devoted 
precisely to the problem at hand, I shall refrain from considering it at 
greater length. 

When I first went to the northwesternmost Amazon in Colombia, I heard 
numerous reports of a strongly hallucinogenic snuff made from the bark of 
forest trees. Known in the area as yakee or paricd^ it was obviously not 
tobacco snuff nor was it prepared from seeds of Anadenanthera. 

After eight years of search, I discovered that yakee was prepared from 
several species of Virola, V. calophylla, V. calophylloidea and, perhaps, V. 
elongata of the Myristicaceae (17, 18) . The natives strip bark from the trunks 
before the sun has risen high enough to heat up the forest. A blood-red resin 
oozes from the inner surface of the bark. It is scraped off with a machete or 
knife and boiled in an earthen pot for hours, until a thick paste is left. This 
paste is allowed to dry and is then pulverized, sifted through a fine cloth, 
and finally added to an equal amount of ashes of the stems of a wild cacao 
species. The ashes give the snuff consistency to withstand the excessive damp- 
ness of the air which might otherwise quickly "melt" the powdered resin- 
paste to a solid lump. 




Fig. 5. — Leaves and flowers of Virola calophijlloidea, one of the species of Virola from 
which a strongly hallucinogenic snufT is prepared. Mitu, Vaup6s, Colombia. Photograph 
by R. E. Schultes. 



300 



Fig. 6. — Puinave Indian preparing yakee-snuff from the red resinous exudate from the 
bark of Virola-trees. Rio Apaporis, Vaupes, Colombia. Photograph by R. E. Schultes. 

At the beginning of this century, the German ethnologist Koch-Griinberg 
mentioned (11) an intoxicating snuff prepared from the bark of an unidenti- 
fied tree by the Yekwana Indians of the headwaters of the Orinoco in Vene- 
zuela. There seems to be every reason to believe that this snuff was made from 
a species of Virola. Seitz {23) has identified the epend snuff of the Waika 
Indians (who now live in the Rio Negro basin of Brazil, but who have mi- 
grated from the headwaters of the Orinoco) as representing Virola calo- 
'phylloidea. 

At one time, I presumed that the active principle in this myristicaceous 
snuff must be the same essential oil — myristicine — that is common through- 
out the family and that has been thought to make nutmeg a dangerous nar- 
cotic in appropriate amounts. Myristicine may have some effect, but Holm- 
stedt has recently isolated tryptamine derivatives from Virola, — snuff which 
itself could account for the hallucinogenic properties of the powder {10). 



301 



It may be interesting to append a few observations which I made person- 
ally after taking yakee {17) . I took about one-third of a teaspoonful in two 
inhalations, using the characteristic V-shaped bird-bone snuflSng tube. This 
represents about one-quarter the dose that a diagnosing medicine man will 
take to bring on an eventual state of unconsciousness. 

The dose was snuffed at five o'clock one afternoon. Within fifteen minutes, 
a drawing sensation was felt over the eyes, followed very shortly by a strong 
tingling in fingers and toes. The drawing sensation in the forehead gave way 
to a strong and constant headache. Within a half hour, the feet and hands 
were numb and sensitivity of the fingertips had disappeared ; walking was 
possible with difficulty, as with beri-beri. I felt nauseated until eight o'clock, 
and experienced lassitude and uneasiness. Shortly after eight, I lay down 
in my hammock, overcome with a drowsiness, which, however, seemed to be 
accompanied by a muscular excitation except in the hands and feet. At about 
nine-thirty, I fell into a fitful sleep which continued, with frequent awaken- 
ings, until morning. The strong headache lasted until noon. A profuse sweat- 
ing and what was probably a slight fever persisted throughout the night. 
The pupils were strongly dilated during the first few hours of the intoxica- 
tion. 

Though performed under primitive conditions in the jungle by myself, 
this experiment does, I think, indicate the great strength of the snuff as a 
psychotropic agent. The witch doctors see visions in color, but I was able to 
experience neither visual hallucinations nor color sensations. The large dose 
used by the witch doctor is enough to put him into a deep but disturbed 
sleep, during which he sees visions and has dreams which, through the wild 
shouts emitted in liis delirium, are interpreted by an assistant. That it is a 
dangerous practice is acknowledged by the witch doctors themselves. They 
report the death, about 15 years ago, of one of their number from the Puinave 
tribe during a yakee-intoxication. 

Sources of Snuffs of Lesser Importance 

We are aware from the literature of references to narcotic snuffs in South 
America the botanical identities of which are still uncertain or unknown. 

A most mysterious snuff of which we still know almost nothing is said to be 
prepared from the fruits of the gigantic moraceous jungle tree Olmedi- 
operebea sclerophylla [19). It is reputedly employed in the central part of 
Brazil, especially along the upper Xingu, but is known only by the general 
Portuguese term rape dos indios ("Indian snuff") . So far as I have been able 
to ascertain, chemical examination of the fruits of this tree has not yielded 
substance with psychotomimetic effects. 

It would be satisfying to know the plant source of the clear amber-coloured 
and aromatic resin that is procured from a large forest tree, and that forms 
part of the sacred accoutrements of every medicine man of the Tukanoan 
tribes in the Apaporis and Vaupes Rivers of Amazonian Colombia (17, 22). 



302 



In particularly difficult cases of diagnosis of disease, divination or other 
magic practice, minute amounts of this resin, powdered, are snuffed. Al- 
though it is said to induce dizziness, it is not reputed to have hallucinogenic 
properties. Nevertheless, botanical identification and chemical study of this 
resin-snuff should be made, if only because of the intriguing fact that it is 
quite generally referred to as paricd, the same name that is applied to the 
highly hallucinogenic snuff prepared from the blood-red resin of the inner 
bark of several species of the myristicaceous tree-genus Virola, by the same 
people in the same part of the Amazon. 

A number of years ago, a missionary working in the headwaters of the 
Orinoco in Venezuela handed me a partially rotted, matted roll of plant 
material which he said was the source of one of the narcotic snuffs of the 
Waika Indians. The condition of the material was very poor, but it seemed 
to represent a species of J^isticia. This identification was tentatively corrobo- 
rated by Dr. E. C. Leonard, the American specialist on the Acanthaceae. 
I have never been able to visit this region to investigate the problem per- 
sonally. With the unsatisfactory preservation of the material and the failure 
of other botanists who had visited the general region to report it {31), I 
more or less dismissed -«/'W,?^2(?/a as a serious contender for inclusion in our 
list of hallucinogens. I am now, however, convinced that this problem must 
be investigated thoroughly in the field, for recently, the Brazilian botanist. 
Prof. J oao MurQa Pires, informed me personally that the Waikas do indeed 
employ a species of Justicia, a species close apparently to /. pectoralis, in the 
preparation of a vision-producing snuff. We know that alkaloids have been 
reported from several species of Justica, and there has been some question 
of synonymy of Jvstica with Adhatoda, which is known to contain harman- 
type alkaloids. Several other genera of the Acanthaceae have been reported as 
alkaloidal, and this family might well bear an intensive phytochemical study. 
In this connexion, I might report here that one of the minor fish poisons 
that I found in use amongst the Taiwanos of the Eio Kananari of Colombian 
Vaupes is the root of an acanthaceous shrub, the genus of which is as yet 
phytochemically wholly unknown : Mendoncia aspera {22) . 

There is, apparently, a fertile field for the study of narcotic snuff prepara- 
tions in the general area of the headwaters of the Orinoco. In fact, this part 
of South America would seem perhaps to represent the centre of com- 
plexity of this curious culture trait. 

The Waikas of. the upper Orinoco basin have been reported to prepare 
their yopo snuff from three plants {27). One source enumerates hisioma, 
Anadenanthera peregHna, as one ingredient; a second is called masho-hara 
or yauardi-Jierm, and is said to be a piperaceous species ; a third is a powder 
known as l)olek-hena. It is a temptation to wonder whether or not this bolek- 
hena or "leaves of the spirit of death" might be a Jmticia. Other sources 
23, 27, 32) assert that the snuff of the Waikas and of a related tribe, the 
Samatari, Avas prepared from the bast of a tree called epena-hesi (referrible 
probably to Virola) ; the ashes of the outer bark of ama-asita, which has 
been identified in the literature as an Acacia; and the powder of masM-Mri, 
a plant of about one foot in height which might conceivably also represent 



303 



Justicia. The Surara and Pakidai make their snuff {30) from seeds of 
Anadenanthem peregrina, ashes of hehurahihend, the bark of a tree of un- 
certain identity but possibly representing also this same species, a piperaceous 
species, maxarahd. The Karime, culturally related to and neighbours of the 
Waikas, eleborate a snuff powder {30) from leaves of "a small plant called 
TiohoimeP Again, are we warranted in suspecting that kokoime might be 

The Kashuena of the Rio Trombetas in Amazonian Brazil, are reported 
by one source to have several kinds of snuff in addition to that made "simply 
of tobacco" (7) . One is prepared by "blending the dried and powdered bark 
of a tree and a quantity of parica with other substances taken from kernels 
or seeds of a variety of wild fruits." A third comprises a mixture of these 
two kinds of snuff. We are left in the dark about the species of tree from 
which the bark is taken, although it may possibly be referrible to an Anade- 
nanthera, and the "wild fruits" remain imidentified. Could one be the fruits 
of Olmedioperebea sclerophylla? 

Final Query 

The several attempts to synthesise and summarise our knowledge of the 
precise botanical identification of plants entering into the preparation of 
South American snuffs {26, 28) have met with the same difficulties that I 
find in trying to discuss this topic here. Because of similarities in the tools 
and methods of snuffing, and especially as a result of the lack of voucher 
botanical specimens, we are too often reduced to conjecture as to the plants 
involved. In view of the importance of snuffing in many cultures — past and 
present — and of the possibility that a number of plants hitherto unknown 
as ingredients of narcotic snuffs might be uncovered, further field investiga- 
tion of snuffs in South America is clearly indicated. 

In connexion with the possibility of finding new plants as sources of nar- 
cotic snuffs, there is one point that has disturbed me for a long time. Why 
should only several of the narcotic plants be administered as snuff ? Snuffing 
is a widespread New World culture trait. It is a relatively easy method of 
self-intoxication. It lends itself easily to ritual or ceremonial use. Snuffs 
usually tend to keep over longer periods, especially in the humid tropics, than 
infusions or decoctions. Why then are not more narcotics taken in this form ? 
One limiting factor, to be sure, would be the requirements that the activite 
principle must be absorbable through the membranes to enter directly into 
the blood stream and be active. Nicotine, of course, answers these reqirements. 
Obviously, the active principles of the snuffs from Anadenanthera peregrina 
and Virola also satisfy these requirements. But would not the active constitu- 
ents of other narcotics likewise follow this pattern ? Why, for example, have 
we never found the sundry species of Datura powdered and employed as 
snuffs ? 

Would snuffs prepared from the bark of Banisteriopsis provide the de- 
sired psychotropic effects? And what about the narcotic properties of Ei^y- 



304 



throxylon Coca — would they be lost if the powdered leaves were introduced 
into the nostrils as a snuff ? The rich variety of toxic plants in the flora of 
South America — would not many of these species have psychotomimetic ef- 
fects which would be more controllable or perhaps less dangerous as snuffs 
then decoctions or infusions of the same plants? All of this leads to two ques- 
tions that I would leave with you : Was not the snuffing of narcotic powders 
much more widely practiced in South America than it is at present? Was and 
is not the number and variety of plants snuffed for their peculiar physiologi- 
cal properties greater than we at present believe ? The answer to both ques- 
tions, I suspect, is "Yes." But only more intensive and extensive search and 
interpretation of the literature, and more immediate and insistent ethno- 
botanical field studies can provide us with answers. 



BIBLIOGRAPHY 

Altschul, Siei von Reis. "A taxonomlc study of the genus Anadenanthera." 

Contrib. Gray Herb., Harvard Univ. 193 (1964), 1. 
Babkeb, James. "Memoria sobre la cultura de los guaika." Bol. Indig. Ven. 1 

(1953), 433. 

Bates, Henry W. "The naturalist on the River Amazons," (1863). John Murray, 
London. 

CJooPEE, John M. "Stimulants and narcotics" in Handbook of South American 
Indians, Bull. No. 143, Vol. 5, Bur. Am. Ethnol. (1949), 525. 

DucKE, Adolpho. "As leguminosas da Amazonia brasileira." Bol. Teen. Inst. Agron. 
Norte 18 (1949). 

DucKE, Adolpho and George A. Black. "Phytogeographical notes on the Brazilian 

Amazon." An. Acad. Bras. 25 (1953) , 1. 
Friekel, ProtXsio. "Mori — a festa do rape (indios kachiryana, rio Trombetas)." 

Bol. Mus. Para. Emilio Goeldi, n.s., Anthrop. 12 (1961), 1. 
Garcilaso de la Vega, (El Inca) "Primera parte' de los commentaries reales. . . 

Pt. 1, Book 2 (1723) , Chapt. 25. 
Goodspeed, Thomas Harper. "The genus Nicotiana" (1954), Chronica Botanica 

Co., Waltham, Mass. 

HoLMSTEDT, Bo. "Tryptamine derivatives in epena, an intoxicating snuff used by 
some South American Indian tribes." Arch. Int. Pharmacodyn. Therap. 156 
(1965), 285. 

Kooh-Grunberg, Theodor. "Zwei Jahre unter den Indianern." 1 (1909) 298. Ernst 
Wasmuth A.-G., Berlin. 

Levi-Stratjss, Claude. "Tribes of the right bank of the Guapore River" in Hand- 
book of South American Indians, Bull. 143, Vol. 3, Bur. Am. Ethnol. (1948), 378. 

Mason, J. Alden. "Use of tobacco in Mexico and South America." Field Mus. Nat. 
Hist. Anthrop. Leafl. 16 (1924) . 

NiMUENDAjt;, Curt (Ed. R. H. Lowie). "The Tukuna" Univ. Oal. Publ. Am. Arch. 
Ethnol. 45 (1952). 

Rowe, John Hovtland. "Inca culture at the time of the Spanish Conquest" in 
Handbook of South American Indians, Bull. 143, Vol. 2, Bur. Am. Ethnol. (1946), 
292. 

Safford, Willlam Edwin. "Identity of cohoba, the narcotic snuff of ancient Haiti." 

Joum. Wash. Acad. Sci. 6 (1916) , 548. 
Schultes, Richard Evans. "A new narcotic snuff from the northwest Amazon." 

Bot. Mus. Leafl., Harvard Univ. 16 (1954) , 241. 
— ' . "Un nouveau tabac h. priser de I'Amazone du nord-ouest." Journ. Agric. 

Trop. Bot. Appl. 1 (1954) , 298. 



305 



{19) ScHULTES, RiCHAED EvANs. "Native narcotics of the New World." Texas Journ. 



Phann.2 (1961)', 141. 

{20) . "Hallucinogenic plants of the New World." Harvard Rev. 1 (1963), 18. 

(21) . "Ein halbes Jahrhundert Ethnobotanik amerikanischer Halluzinogene." 

Planta Medica 13 (1965) , 124. 
{22) . "The search for new natural hullucinogens." Lloydia 29 (1966), 293. 



{23) Seitz, Geoeg. "Einige Bemerkungen zur Anwendung and Wirkungsweise des 
Epend — Schnupfpulvers der Waika — Indianer." Ethnolog. Studier No. 28 (1965), 
117. 

(2^) Spktjce, Richabd (Ed. A. R. Wallace). "Notes of a botanist on the Amazon and 

Andes." 2 (1908) , 426. Macmlllan & Co., Ltd., London. 
(25) voN Reis, Siri S. P. "The genus Anadenanthera : a taxomomic and ethnobotanical 

study." Ph. D. Thesis (ined.) (1961), Radcliffe College, Cambridge, Mass. 
{26) Wassen, S. Heney. "Some general viewpoints in the study of native drugs, espe- 



cially from the West Indies and South America." Ethnos 29 (1964), 97. 

(27) . "The use of some specific kinds of South American Indian snuff and related 

paraphernalia." Ethnolog. Stud. 28 (1965). 

(28) . "Sydamerikanska snusdroger." Nytt och Nyttigt, No. 1 (1966), 1. 

(29) and Bo Holmstedt. "The use of parica, an ethnological and pharmacological 



review." Ethnos 28 (1963) , 5. 
{30) WiLBEET, Johannes. "Indies de la regidn Orinoco — Ventuari." Monografia No. 8, 

Fundaci6n La Salle de Ciencias Naturales, Caracas (1963) . 
{31) WuKDACK, John. "Indian narcotics in southern Venezuela." Gard. Journ. 8 (1958), 

116. 

{32) Zeeeies, Otto. "Das Lasha — Fe^t der Waika — Indianer." Di Umshau 21 (1955), 
662. Frankfurt-am-Main. 



306 



Vilca and its Use 



SiRi VON Reis Altschul 

Botanical Museum of Harvard University, Cambridge, Mass. 

It generally has been assumed that the Peruvian substance known as 
Vilca is, or was, a snuff made from a Piptadenia in the family Leffuminosae 
(Safford, 1916; and later authors). However, there is evidence in the litera- 
ture and in unpublished materials that Vilca may involve other plants as 
well, and that it may have been used in forms different from snuff. I would 
like to examine this evidence with a view to opening new areas in the search 
for psycho-active drugs. 

The discussion which follows is based in part on research in the ethno- 
botany of the strictly New World genus Anadenanthera, which formerly 
was considered as section Niopa of the genus Piptadenia and is known com- 
monly as the source of some hallucinogenic snuffs. The genus Anadenan- 
thera contains two very similar species which have not been shown to differ 
significantly with respect to their psycho- activity, and which may have been 
used interchangeably. One species is Anadenanthera colubHna., found in 
southern Peru, Bolivia, northern Argentina, Paraguay and southern Brazil. 
The other species is A. peregrina, ranging from southeastern Brazil to the 
Greater Antilles, (von Reis, 1961 ; von Reis Altschul, 1964) . 

The discussion also will make use of information which recently has be- 
come available. This information has been selected from nearly 6,000 field 
notes from a search of almost 2,500,000 herbarium specimens at Harvard 
University (von Reis, 1962). Dr. Richard Evans Schultes and I have just 
completed this project and intend to publish our data as soon as it is feasible.^ 

Let us look first at the earliest references to Vilca, which are to be found not 
in the herbarium but in the post-conquest literature of Peru. Around 1571, 
Polo de Ondegardo reported that the witch doctors of the Incas ' foretold 
the future by speaking with the devil in some dark place by means of various 
ceremonies, for which office they intoxicated themselves with an herb called 
Villca, pouring its juice into chicha or taking it another way. The reporter 
stated that, although only old women were reputed to practice this craft, in 
fact its use was widespread but concealed among men and boys, as well. In 
1695, Santa Cruz Pachacuti spoke of a medicine called villca which was the 
seed of a tree. Two years later, Gonzalez Holguin said that Villca referred to 
a tree with a purgative fruit. An early report by Falcon (1946 ed. ; in Yacov- 
leff & Herrera, 1935) indicated that the Indians took a purge called Vilcas 

^This project was carried out through the sponsorship of The Botanical Museum of Harvard 
University. It was supported by Smith, Kline & French Laboratories ; the National Institute of 
Mental Health ; and the Lilly Research Laboratories. We are very grateful to the staffs of the Gray 
Herbarium and Arnold Arboretum of Harvard University, especially to Professors Reed C. Rollins 
and Richard A. Howard, respective directors, for generous permission to use their facilities and 
herbarium materials. 

^Murdock's Outline of South American Cultures (1951) has been used for classifying all the 
Indian cultures dealt with in this paper. 



307 



(or elilcas) which was beneficial to those who worked too hard. In 1629, 
Vasquez de Espinosa said that the pods of the vilca tree had small, round 
seeds which were the common purge of the Indians for all sorts of humors. 
Some years later, in 1653, Bemabe Cobo stated that the Indians used a de- 
coction of the roots of a Polypodium. fern with two or three Yilca. seeds to 
remove phlegm and choler without pain or nausea. He gave a fair, but not 
diagnostically adequate, description of the tree called Vilca, and maintained 
that the Indians cured a variety of illnesses with the purgative seeds taken 
in cMcha. These seeds were said to be both laxative and emetic and to dis- 
pel melancholy. Cooked and drunk in honey, they cleared the chest, stimu- 
lated urination and made women fruitful. 

Modern writers usually identify the name Vilca with the species here 
called Anadenanthera colvhrina (Herrera, 1934; Lastres, 1951). In 1916, 
Safford stated that seeds labelled Huillca and secured from an Indian drug 
vender in southern Peru had been identified as belonging to Anadenanthera. 
Herrera reported in 1940 that the seeds of Huillca [Herrera 3210) are a 
narcotic-cathartic element in the indigenous pharmacopoeia. Yacovleff & 
Herrera (1935) have said that the seeds are sold as purgatives in the local 
markets. Recently, Vargas confirmed in a letter (1966) from Cuzco that herb 
doctors in that vicinity continue to use the seeds for this purpose. Cardenas 
has stated from Bolivia that the same species, known as Willca, is used as a 
stimulant and aphrodisiac by the callahuayos (1943), or itiaerant medicine 
men who travel today between Chile and Mexico (H. C. Cutler in conversa- 
tion, 1966) . The seeds also have been used in our time as charms or fetishes 
by the Quechua Indians of northwest Bolivia. At the market in La Paz one 
may buy, among other goods for similar purposes, seeds of A. colubrina and 
of other leguminous species in the genus Ormosia. These seeds and other 
items are buried, for magical purposes, under houses in the process of con- 
struction (Nordenskiold, 1907; Pardal, 1937). 

In the course of the herbarium search mentioned above, we found two 
specimens labelled Vilca. Both belonged to Anadenanthera colubrina. One 
was from southern Peru (Departamento de Huancaveiica, Weherbav^r 6605) . 
The other was from east of La Paz, Bolivia (Canamina, White 25 Ji). These 
data indicate that A. colubrina indeed is identifiable with Vilca, but they do 
not insure that Vilca is referable exclusively to this plant. 

For one thing, it is especially difficult to establish botanical identifications 
in the early literature. Apparent inconsistencies or omissions in plant descrip- 
tions, and the lack of voucher specimens require that we habitually entertain 
the possibility of altogether new interpretations, particularly among groups 
like the legiunes, where many similar species may be mistaken one for another. 
In fact, the widespread representation of the Leguminosae in native medi- 
cine suggests that a pharmacological screening of its New World genera for 
psycho-active compounds might be a worthwhile undertaking. 

In conjunction with our herbarium search at Harvard, we found three 
species with common names similar to Vilca but from families other than the 
legumes. These were a Peruvian specimen of Banisteria leiocarpa {Mal- 
pighiaceae, Vargas WW) labelled Vilca bejuco, or climbing Vilca; a Vene- 



308 



zuelan specimen of Virola sebifera (Myristicaceae, Steyermark 60758a) 
labelled toircaweijek, whose inner bark is said to be dried and smoked by witcli 
doctors to cure fevers; and a Peruvian specimen of Baccharis floribunda 
{Ovmpositae, West 3735) labelled UllccocMlca, a species also reputedly cura- 
tive {Macbride & Featherstone 1631 ) 

In addition to these interesting attributions, our herbarium search re- 
vealed information which does not relate directly to Vilca but which I will 
present here because it very much bears upon the search for psychoactive 
drugs. This information consists of common names of Anadenanthera species 
which have come to light in connection with new plants. The accompanying 
map (Fig. 1) shows the distribution of the conunon names of Anadenanthera 
species in South America, based upon labels of specimens examined. With 
these names and their locations in mind, I would suggest that the following 
species be examined chemically for possible pharmacological activity : in the 
Asclepiadaceae^ Asdepias curupi (Balansa 1361) from Paraguay, labelled 
Curwpi, the powdered leaves and a decoction of the plant said to be applied to 
snake bite; in the Euphorhiaceae, three species of Sapium from Uruguay, 
labelled Curupi (S. gibertii, Lomhardo 301/3 ; S. haematospermum, Lombardo 
30Jf,7 ; S. linearifolium, Lombardo 33Ji.Ii.) ; in the Rubiaceae^ Guettarda vibur- 
noides from Brazil, labelled Angico {Mexia 5583) ; and in the Leguminosae 
from Brazil an undetermined Pithecellobium {Krukoff 1887), Piptadenia 
contorta {Mexia ^28), both labelled Angico Branco; and Mimosa malaco- 
centra {Mexia 56£4-) labelled Angiguin, whose leaves are used to make a tea 
for pain. 

Further afield from Anadenanthera but pertinent to the objectives of the 
conference are a few surprising new combinations : in the C onvolvulaceae : 
two species of Ipomoea {I. denticulata, I. tiliacea, W. H. & B. T. Hodge 
3323, 3318, respectively) from the island of Dominica, West Indies, labelled 
Gaapi; in the Leguminosae, Calliandra calothyrsis {Standley 238^6) and 
Leucaena guatemalensis {Standley 7 3562) , both from Guatemala and labelled 
Yaje; in the Compositae, Trichocline incana {Meyer 3982) from Argentina, 
labelled Coro and said to be smoked with tobacco. The word Coro has ap- 
peared now and then in the early chronicles and has been linked previously 
with Anadenanthera and (the root of) wild tobacco (Cobo, 1890-93 ed. ; 
Uhle, 1898) but never, to my knowledge, with this plant : According to Cobo, 
Coro powder was drunk in water for detention of urine, or taken as snuff 
for headache and to clear the vision. 

I would like to return now to Vilca and to review some of the botanical 
common names similar to it in the published literature. The species ascribed 
to these names perhaps should receive critical attention, too. Vilcardn has 
been associated with Piptadenia rigida (Burkart, 1949) in Argentina. Vil- 
caparu is a word for yellow maize (Gonzalez Holguin, 1607) from Bolivia 
(A. Grobman in conversation, 1961) . HuiUTco means species of Ipomoea and 

' Any pharmacological research on these and other species cited in this paper should be preceded 
by a verification, by a competent botanist, of the correct identification of the specimens cited. 
The research should be based on the specimen cited, as designated by the collector's name and field 
number. All specimens are in the collections of the Arnold Arboretum and Gray Herbarium of 
Harvard University, Cambridge, Mass. 



309 




Fig. 1 



the Nyctaginaceous genus Mirabilis (Herrera, 1934). Tara Huillca has been 
identified, as Anadenanthera colubrina (Yacovleff & Herrera, 1935), but 
Tara, alone, refers to another legume, Oaesalpinia tinctoria (Herrera, 1934) . 
Wilca Tarwi has been assoicated with the leguminous genus Lupinm (Lastres, 
1941) . The chronicler Poma de Ayala (1936 ed. ; Lastres, 1941) reported that 
the Indians purged themselves once a month with liilca tauri, made from 
some kind of seeds ground into a liquid, half of which was drunk and half 
of which was taken as an enema which was said to give the Incas strength, 
health and a 200 years life span. At the time of the conquest, the word 
Vilcu referred in Aymara to a plant with yellow, bird-like flowers (Gobo, 



310 



1890 ed., Vol. I). It also meant ivy (Villcu) Gonzalez Holgrnn, 1607). Our 
herbariiim search unearthed two specimens of the climbing Compositae, 
Mikania cordifolia {Mexia 801^2) from Peru labelled Huaco verde, and M. 
Jumstoniana {Gaec. et Ed. Seler 51^75 (396)) from the ruins of Palenque, 
Mexico. Villca or Huacca both meant idol (Gonzalez Holguin, 1607) or 
something sacred to the Incas. Hence, the possibility that Mikania species 
might have been ritual plants deserves a thought. 

One might sum up what generally has been known of the role of Vilca 
in Peru at the time of the conquest by saying that it seemed to be confined 
mostly to simple folk-medicine, its divinatory aspects divorced from formal- 
ized religion. Eowe has stated (in Steward, 1946) that narcotics were im- 
important to the Inca culture and that none was taken expressly to obtain 
visions; the strongest substances reputedly used were coca, tobacco and 
Vilca. The main curatives were Ghicha, Vilca and tobacco (Fornee, 1885 ed.) , 
and Peruvian medicine consisted primarily in blood-letting, purging with 
Vilca, and in taking tobacco {sayri) snuff (Garcilaso de la Vega, 1688 ed.). 

Besides its occurrence with reference to medical botany, the term Vilca 
appears so frequently and in such a variety of contexts in the historical nar- 
ratives of Peru that one is led to suspect that it may have had a great 
antiquity and that plants passing under its name may have had greater 
ritual importance in earlier times than at the time of the conquest. Various 
forms of the word meant enema or clyster {Vilca or Vilcas in Gonzalez 
Holguln, 1607; Vilca Tarvi or Vilcatauri in Lastres, 1941; Vilcachima in 
Lastres, 1951; Vilcana in Gonzalez Holguin, 1607, Lavoreria, 1902, Mossi, 
1860) ; the giving of an enema (Vilcani in D'Harcourt, 1939, Gonzalez Hol- 
guin, 1607, Mossi, 1860, Lavoreria, 1902) ; a syringe (Vilcana in Mossi, 
1860; uilcachina in Poma de Ayala, 1936 ed., Lastres, 1951) ; or a small 
stick commonly used to clean the rectum in the Cuzco area (Vilcachina in 
Lastres, 1951). The same root is found in the words for doctor or surgeon 
(Vilca-Oama in Velasco, 1840 ed.) ; priest or informant {V iliac in Lastres, 
1951) ; and ostrich-like chief (Surivilca in Lastres, 1941) ; and in designa- 
tions of familial relationships (Vilca or Vilcay in Gonzalez Holguln, 1607, 
in Mossi, 1857, 1860) . In 1671, Ogilby stated that in the Chilean language 
Vilca meant mother-in-law ; " Hilca meant one-eyed person. Among the 
Araucanians, a pivillca was a flute (Medina, 1882) . In the area of the Dia- 
guita culture, Vilka is today a surname of Quechua or Calchaqui origin 
(Ambrosetti, 1917) . 

Essentially, however, Vilca was one of the two names mentioned earlier 
by which the Peruvian Indians called their idols or gods. It was used 
to describe whatever was first, original or important (Lastres, 1941), and 
to refer to any sacred place or thing (Cobo, 1890-93 ed.; Garcilaso de la 
Vega, 1688 ed., 1941^ ed.; Gonzalez Holguin, 1607; Mossi, 1860). These 
include words for an idol (Huacavilca in Lastres, 1941), a temple (Hvxi- 
rivilca in Cieza de Leon, 1864 ed.), a town or village (Vilca or Vilcas in 
Cobo, 1890-93 ed.), bodies of water (Vilca or Vilcas, a river in Garcilaso de 
la Vega, 1688 ed. ; Vilca-Mayo, a river in St. Cricq, 1873-74 ed. Vilca-cocha, 
a lake which flows into the Vilca-Mayo in St. Cricq, 1873-74 ed.), a valley 



311 



called the Paradise of Peru {Vilca-Mayo in Cieza de Leon, 1864 ed.), a 
mountain peak {Vilcanota in Garcilaso de la Vega, 1688 ed., 1941-i4 ed. ; 
Hucmca Vilca in Lastres, 1941; Vilcaconga in Cobo, 1890-93 ed.) or a sierra 
{Vilca or Vilcas, Vilcanota in Cobo 1890-93 ed.), a province (Vilca Pampa 
in Cobo, 1890-93 ed., Garcilaso de la Vega, 1688 ed., 1941-44 ed. ; Vilca or 
Vilcas in Cobo, 1890-93 ed., Cieza de Leon, 1864 ed.) or a people {Vilca or 
Vilcas in Garcilaso de la Vega, 1688 ed., 1941-44 ed. ; Chumbivilcas in Cobo, 
1890-93 ed., Garcilaso de la Vega, 1688 ed., 1941-44 ed. ; Huancamlca in 
Cieza de Leon, 1864 ed.) . 

Among the ritual paraphernalia which seem to relate to Vilca are the vilca 
ronco (Gonzalez Holguin, 1607) , small coca- filled baskets which were thrown 
into the fire at animal sacrifices in Cuzco. One might mention, also, the vilques, 
earthenware jugs with which the Indians toasted their dead, after which 
the chicha contained in them was poured over a round stone which they 
worshipped in the middle of a plaza (Cobo, 1890-93 ed.). The chronicler 
Acosta (1584, folio 104) relates that the Spanish conquerors ordered the 
Incas to stop worshipping the sun, moon and so on, ". . . ni tengays villcas, 
ni guacas, ni figura de hombre, . . ." 

An Incaic version of the origin of the medicinal Vilca (Santa Cruz 
Pachacuti, 1927 ed. ; Yacovleff & Herrera, 1935) states that an Inca captain 
named Villcaquire^ being struck down in war by his nation's enemies, the 
Chanca, requested that he be buried in the trunk of a nearby tree which, 
he foretold, would produce villca seeds, io dispell all bad humors and choler 
from his people. The story takes place above a river on the Aporima road. 
Specimens of Anadenanthera colubrina {West 3679, 38Jfo) have been iden- 
tified from the Department of Apurimac. I would not be surprised to 
learn that the story was a relatively modern one which served the needs 
of the Incas to attribute to their own invention something which had its 
origins in much earlier times. It is tempting to wonder whether the medicinal 
Vilca had had an important role among the people named Vilca, who were 
numbered among the Chanca (Garcilaso de la Vega, 1688 ed.). Legend 
has associated the Vilca with edifices whose art and grandeur, built cen- 
turies before the Inca monarchy, was much admired and emulated by the 
Inca culture (Cobo, 1890-93 ed.) . 

Modern archaeology has cast doubt as to the veracity of some of the his- 
tories in the early narratives, and, geographically, it is not easy to locate 
many of the places referred to in the sixteenth and seventeenth century 
writings on Peru. However, a number of names incorporating the term 
Vilca can be found today on a map of southern Peru, correlating in general 
with the distribution of Anadenanthera in that country. 

Archaeological data suggest that the use of enemas was more widespread 
in pre-conquest times than it was when the Spaniards arrived (Heizer, 1944 ; 
Nordenskiold, 1930; Velez-Lopez, 1930). What was used in these enemas 
and in the tubes and tablets of the neighboring regions has not been deter- 
mined, to my knowledge. Anadenanthera seeds have not been foimd at any 
Peruvian sites, as far as I know. The Getil snuffs used at the time of contact 
among the Mataco and Vilela cultures of northern Argentina appear to 



312 



have been Anadenanthera-deTiyed. But tlie use of this genus further south 
beyond its natural distribution is less likely. Yet there, further south, the 
Comechingon Indians took something called Sehil through the nose (Sotelo 
Narvaez, 1915 ed.), and the Huarpe Indians chewed a substance called Gibil 
for endurance (Ovalle, 1703). Perhaps one even should ask whether the 
monumental weeping god with the tear-streaked cheeks at Tiahuanaco m 
Bolivia might be depicted in a state of intoxication from a powerful snuff 
or emetic. 

This paper has posed many more questions than it has attempted to 
answer, but it has been instrumental in pointing out some unusual approaches 
to a better knowledge of Vilca, which could serve as a model for studies 
on other little known so-called narcotics. The facts gathered here suggest 
that a number of hitherto unsuspected species should be analyzed for psycho- 
activity, and that the drug plants used by man in the New World may 
prove to constitute a richer and more elaborate complex than we yet have 
been led to believe. The early writings deserve to be read again, and her- 
barium information should be sought more assiduously. 

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Off., 1946. 

Uhle, M. "A snufflng-tube from Tiahuanaco." Bull. Free Mus. Sci. Art 1 : 158-177, 1898. 
Vaegas, O. Personal communication, Nov. 10, 1966. 

Vasquez de Espinosa, a. "Compendium and Description of the West Indies." Smith. Misc. 

Coll. 102 : 1-862, 1942 ed. 
Velasco, J. DE. Histoire du Royaume de Quito 1 : 164. Paris, 1840 ed. 
■V£lez-L6pez, L. "El cllster en el antiguo Peru." Proc. Intern. Congr. Am. 23 : 296-297, 

1930. 

Yacovleff, E. & Heebeea, F. L. "El mundo vegetal de los antiguos peruanos." Rev. Mus. 
Nac. 4: 31-102, 1935. 



314 



Epena, the Intoxicating Snuff 
Powder of the Waika Indians 
and the Tucano Medicine 
Man, Agostino ' 

George J. Seitz 

Koln-Lindenthal, Diirenerstrasse 175, Germany 

The WAIKA Indians belong to an isolated group of natives called YANO- 
AMA or YANONAMI. They live in the triangle formed by the Eio Brarico 
in the southeast, the Uraricuera and Upper Orinoco Eivers in the north and 
the Rio Negro in the southwest. This territory lies on both sides of the bound- 
ary between Brazil and Venezuela. 

During the last ten years, my wife and I made six expeditions to several 
WAIKA tribes in the region of the Upper Rio Negro, that is the southwest- 
ern part of that habitat, situated in the Brazilian Territory near the Vene- 
zuelan boundary. We found these tribes 

(1) near the TUCANO IGARAPfi, one of the headwaters of the Caua- 
bori River, 

(2) on the Maturaca Channel, in the south of the Fall of HUA, 

( 3 ) on the Marauia River, near the Igarape IRAPIRAPl and 

(4) on the Upper Maia River, a branch of the Cauabori River. 

These Indians are nomads. We had a lot of difficulties in finding them and 
their primitive villages, called "SHABONO". They are always rather dis- 
tant from the rivers, and we had to march hours and hours through the thick 
jungle to reach them. 

Without the assistance and the experience of a Catholic priest — the only 
Avhite man who had made contact with the WAIKA Indians before — our 
expeditions scarcely would have been successful. 

The name WAIKA means KILLER — a nice, gentle sort of name. Un- 
doubtedly, the group is one of the most primitive in South America. They 
have never found out how to make a boat or a raft. As nomads, these Indians 
make pots ; they do not know anything about alcoholic drinks, or mandioc, 
the most important vegetable of the southern Hemisphere besides corn. 

In a region where the rivers provide the most important traffic routes, they 
have never found out how to make a boat or a raft. As nomads, these Indians 
wander about the jimgle. They live in primitive, wall-less, palm-thatched 
huts only as long as the food lasts in the neighborhood. When they eat up 
aU the food around, they go to another village with huts just as primitive. 
They are a restless people that live off the land. And they live in a period 
that for us is prehistoric. 

^The presentation of this paper was given In conjunction with the showing of an excellent, 
Informative film. The photographs In this paper come from this film. (Editor) 



315 



They have never learned anything from their more advanced neighbors, 
the ARUAK group, represented by the TUCANO and BANIVA tribes. 

The existence of these WAIKA Indians has been known for more than a 
hundred years. However, explorers of the region — Humboldt, and at the be- 
ginning of our century, Koch-Griinberg and Hamilton Eice — gave only brief 
reports about the WAIKAS. They had only occasional meetings with a few 
Indians from this group. These quick meetings did not give any basis for 
more than superficial notes. 

In general, the explorers knew about the WAIKAS from the stories of 
other Indians, who described the Indians as terrible enemies, who used their 
poisoned arrows to keep out trespassers. 

In the Brazilian territory, the WAIKAS made their first mark in modern 
history in 1929, when they attacked the settlements of rubber-tappers in the 
area between the Imeri Range and the Upper Rio Negro — along the Demiti, 
Cauabori, Marauia and Padauirl Rivers. The Indians attacked suddenly, 
killed the men and carried off the women and children. The survivors fled to 
the Rio Negro. For 25 years, until 1954, everybody kept away from the area 
for fear of the Indians. In 1954, a Catholic priest of the Salesian mission in 
Tapuruquara, Rev. Antonio Goes, entered the territory, went up the Caua- 
bori River by boat and made the first peaceable contact with a tribe of the 
WAIKAS. 

We met the priest in 1955 when we went through Tapuruquara on an expe- 
dition to the Colombian frontier. One year later, in 1956, we went with him 
to the WAIKA village situated near the headwaters of the Cauabori River, 
a few miles from the Venezuelan boundary. 

It was the priest's third visit to the tribe, where we found about 200 In- 
dians in their original, primitive state. They never had any previous contact 
with civilized people other than the priest and then, ourselves. 

In two later visits, we were able to observe and to film their daily village 
life, but we saw nothing of the snuff. We saw them dancing under the in- 
fluence of the EPfiNA, but we were not able to see the snuff prepared. When 
we asked, they told us that the ingredients did not grow nearby. 

Our relations improved with the repeated visits. On our fourth trip in 1960, 
we were received like old friends. We were shown the ingredients. We saw 
that they were neither seeds of PIPTADENIA PEREGRINA nor of any 
other tree. Tliey turned out to be two kinds of bark and the leaves of a small 
plant. For the first time, we Avere able to get some of the snuff by exchanging 
gifts. It was the same powder that I sent to Professor Holmstedt, who 
analysed it. He found tryptamine derivatives to be the active components. 
In 1965, finally, we had a chance to film the snuff-making process. 

The Preparation of the Epena Snuff-Powder 

We could observe and film the whole process of the EPfiNA preparation 
on the Upper Marauia River in the village of the KARAUETARI tribe. 
First we looked, in the company of two Indians, for a tree of the species 



316 




Fig. 1.— a sapling of "EPENA." 



VmOLA CALLOPHYLLOIDEA, Markgraf, called by the Indians 
EPfiNA. 

We had started in the early morning because the Indians said that the 
bark has to be stripped in the early hours of the day for the snuff powder to be 
good. The EPfiNA trees did not exist in any quantity. We marched three 
days through the jungle to find a group of them. 

When the bark is stripped it appears white on its inner-side, but only a 
few seconds later a red brownish resin like liquid begins to exude in drops. 
The Indians told us that this "bleeding" is more intensive before the heat 
of the tropical sun begins to penetrate the forest. 

The inner-side of the bark consists in a soft fibre-like layer that the Indians 
scrape off with a knife. These scrapings — moistened by the red brownish 
liquid — are collected on a palm-leaf and carried to the village for drying. 



317 



Th.e drying process begins very slowly. The scrapings are fastened on a 
twisted disk which will be put approximately four feet above a slow fire, and 
there remain till the next morning. Then comes the second phase of the 
drying, more intensive, directly over the fire. 

In this state the scrapings are stored till the second ingredient of the 
snuff -powder, called AMA ASITA, is ready. AMA ASITA is a tall tree that 
was not possible to classify as yet. But it seems to be a TEICHILIA species. 
Also, this tree seems to be scarce. 

Before stripping the Indians looked for a specimen with smooth bark. 
They took only strips of bark whose outside was entirely perfect. This 
outside is important. It is the only part used. It was separated from the inner 
side of the bark immediately after the stripping and carried to the village. 
There these outside strips of the bark were cut in pieces and put in a fire. 
As soon as they began to glow, the Indians took them out of the fire and let 
them burn to ashes separately. They watched carefully, to see that no piece 
of any other wood or bark might be mixed with them. 




Fig. 2.— Stripping of the "EPfiNA" bark. 

318 



Fig. 3. — Only a few seconds after the stripping the red-brownish liquid begins to exude 
in drops and tinges the clearsighted wood of the trunk and the inner side of the bark. 

These ashes of the AMA ASITA-bark are called by the WAIKA-Indians, 
"YUPU USHI". 

While the bark was burning separately, our Indian began to rub down 
the dried EPfiNA scrapings with his hands. He did it sitting on the ground 
and pressing his knees against his hands. 

After reducing the EPfiNA scrapings to a crumbled dust, the Indian 
roasted it for a short time over the fire. Then he mixed it with the ashes of 
AMA ASITA. The proportion of the mixture was 50 : 50. As it is measured 
by sight, the snuff-powders of the different manufacturers never have the 
same tone of colour. 

The snuff was not yet sufficiently uniform and refined. It contained little 
spelts and crumbs that had to be eliminated. This was done in a little basket 
such as each WAIKA household owned. The Indian beat the basket gently, 
and the resulting dust was the final snuff -powder. It was kept in a bamboo- 
tube, the usual storage box of the WAIKAS. Four or five of these tubes are 
stuck between the palm-tree-leaves of each hut. The smaller tubes are usually 
used for snuff-powder, and the bigger ones for keeping feathers, arrow-heads 
and pigment for painting the body. 



319 



Fig. 4. — The inner side of the bark consists in a soft fibre-like layer that the Indians 

scrape off with a knife. 



320 




Fig. 5.— a branch of AMA ASITA. 



321 



Fig. 6. — -The AMA ASITA bark is stripped. Note that the wood of the trunk remains 

clear-sighted. 



322 



Fig. 7. — The outside of the bark is separated from its inner side. 



323 




Fig. 9. — The dried "EPENA" scrapings are rubbed down with the hands. 



325 



In another WAIKA-village, near the Maturaca-channel, we saw that a 
third ingredient was added : the little leaves of a HEEBACEUS-plant, called 
MASHI HIEI, like the EPfiNA -scrapings dried and powdered. These leaves, 
however, have no intoxicating effect. The Indians say they are merely 
aromatic. I don't know why the KAKAUETARY didn't use the plant. 
Perhaps it was not available at the moment, or the Indians in the MA- 
RAUIA-Eiver like another flavour.^ 

1 There is also used another snuff powder which contains, besides the above mentioned three 
Ingredients, the other vegetables : 

(1) The leaves of a plant called POSCHI-HAVE-MOSCHI-Hena ("hena" means "leaf") 

(2) The leaves of another vegetable called AI-AMO-Hena. 

In the villages we visited, the Indians either could not or did not want to show us these two plants. 
They always said that they only grew In the higher region of the mountains, and not nearby. For 
this reason the powder compound of the five ingredients was not on hand. 

In my opinion it is the same compound whose snuffing we saw in our first expedition, and whose 
effect was discribed as noxious for health. (People of the rain forest, page 167.) I cannot at the 
moment say more about this powder. Neither the missionary with whom I am corresponding and 
who lives in continued contact with several tribes, nor myself, saw in our other expeditions a 
similar effect again. And in no other visited tribe were we able to get this powder. 




Fig. 10. — The Indian sifts the "EPfiNA" in order to eliminate spelts and crumbs. 
326 




Fig. 11. — The final snufif powder is stored in a bamboo tube. 



Some Remarks on the Use of Epena 

We watched the use of EPfiNA in four WAIKA- villages : (1) near the 
Upper Cauabori River ; (2) near the Upper Maia River ; (3) near the Upper 
Marauia River, and (4) near the Maturaca Channel. 

Firstly: The snuff was never inhaled in the morning. At this time, we 
saw some of the corresponding preparations, such as painting the face and 
the upper part of the body. Another Indian helped to paint the back and 
legs. The feather ornament is tied on the upper arm. All in all a certain 
festive preparation is part of the ceremony. 

Secondly, The snuff-Inhaling ceremony generally began in the early after- 
noon ; rarely in the evening. 

Thirdly : Once, we saw two Indians blow snuff into each other's noses. Gen- 
erally, only one person inhaled the EPfiNA. 



327 



Fourthly: Only adult men, but not women, took part in the ceremony. 

Fifthly : The blowpipe, 23 to 28 inches in length, was used for inhalation 
with one exception. We did not see any other inhalation instrument. 

Sixthly : Only once did we see an Indian inhale snuff without the aid of 
another man, and without instrument. (See also footnote Nr. 4) . He poured 
the snuff from the bamboo tube into his open hand, lifted his hand to his 
nose and inhaled the powder simply and neatly. 

Seventhly : When we became able to distinguish one Indian from another, 
we saw that there is no system for the snuff ceremony. For example : There 
were Indians who took EPfiNA powder every day at any time in the after- 
noon; there were others who practiced the ceremony only once in a fort- 
night. Seldom did we see any formal motive for taking the snuff, such as 
curing a sick person, invoking success in the'hunt or thanksgiving for a suc- 
cessful hunt. 

Only for the first motive, we saw snuff taking a few times. One or two men 
took snuff to bring about the curing of a sick child. So did the child's father, 
but not at the same time. I had the impression that in most cases, snuff was 
taken without any profound meaning — such as treating the ill, exorcism, con- 
tact with the HAKULA spirits, cult. There seemed to be only a sort of 
swagger — an attempt to show "What a great guy I am !" 

Otherwise how can we explain the fact that a great number of the Indians 
did not take any notice of the ceremony in the village square. Or that a 
dancer's girl friend sitting in her hammock, proudly watched the man 
stamping and yelling in front of the hut? Moreover, the interpreters occa- 
sionally burst out laughing at the dancer's movements and words. These 
words did not always seem to make sense. 

The dose for inhaling in each nostril was a coffee-spoon full. The Indians 
usually take two doses. Only once, in the KARAUETAEI-village near the 
Marauia River, did we see an Indian take four doses, one after another. 

Administration 

The inhalation was practiced in general in the following manner: (with 
one exception observed in the KAUARETARI-village) : At first the snuff 
power of one or two bamboo tubes was poured on a little board or plate, and 
the little crumbs — caused by the high humidity of the air — were carefully 
pinched between the fingers. 

Then the two Indians, the carefully painted and adorned one as well as 
the "blower" cowered under the roof of a hut, one opposite the other. The 
"blower" filled a dose of powder with his fingers in the blowpipe, which the 
other Indian kept on his right nostril. With a forceful blow the powder 
entered the nose. The receiver immediately let fall the blow-pipe and held 
the back of his head with both hands. 

Our interpreter, a Portuguese speaking Indian, explained that he would 
feel in this moment a violent headache. Not seldom, the Indian curved him- 
self, probably because of this headache. Saliva ran out his mouth and he 
vomited. 



328 




Fig. 12. — With a forceful blow the powder entered the nose. 



After about 3 or 4 minutes it seemed that the first effect passed, and he 
took again the blow-pipe, which the other Indian, the "blower", had again 
filled up. The Indian now put the blow-pipe on the left nostril and got the 
second dose. The immediate consequences like headache, salivation and vom- 
iting were repeated, however, not always so strongly. 

Effect 

After inhaling the two doses of EPENA, the usual quantity of snuff 
powder at the beginning of the ceremony, the Indian continued for about two 
or three minutes in his cowered position. Then he stood up and walked 
swaying like a drunkard. On his way his walk became faster and steadier. 
His stare became fixed and he experienced a violent perspiration. In a few 
minutes his face and body were completely wet. 

Then his steps changed into a stamping that generally was adapted to a 
certain rhythm: three or four steps forward, one step on the same place. 
This "dance" the man accompanied with a recitative, monotonous singing, 
which was relieved about every five to eight minutes by a terrible yell. During 

329 

262-016 0-67— 23 



Fig. 13. — Saliva ran out of his mouth and he vomited. 



this yelling the man generally stopped his "dance," and turned himself with 
high lifted or spread arms to the mountain-range that elevates itself, steep 
in the sky, a few miles to the north of the villages.^- ^ 

After about half an hour of stamping and singing and yelling an interval 
took place in most of the observed cases. The Indian stood some minutes 
with straddled legs, the upper part of his body bowed forward, nearly the 
position which we took as children for playing leap frog. After this interval, 
either the singing and stamping continued or the Indian — still singing and 



2 In some of the cases observed by us, this yelling toward the mountain range certainly was a 
threat against another tribe, living In hostility against our Indians. Some weeks ago they had 
killed two members of that tribe and expected now the requital attack. 

1 see in these yelllngs against the mountains where the other tribe was living, no Invitation to 
the HAKULA spirits for help, but translate them more In this way : 

"Come on over when you get up the courage ! — We will make hash of you !" Conclusion : Nothing 
but boasting, in consequence of the macropsla provoked by the EP£!NA. Certainly, this makes the 
dancer think he Is physically superior. 

2 In the cases when they had inhaled EPfiNA to cure a sick child, the dance was stopped in front 
of the child's hammock, and the Indian accompanied his yells with the vehement movements of 
his arms, or the softly passing of his hands over the child's body. So, he tried to take out the Illness 
of the patient's body. 



.330 



stamping — fetched from his hut some arrows, and continued dancing with 
these.* 

The snuff powder EPfiNA provokes a strong intoxication but by no means 
an entire state of trance. Otherwise the man would not be able during his 
"dance" to find with sure hand the arrows in the hut or — as it had happened 
with me when I had gone with the camera in spite of warning — would have 

« The Indian of the KARAUETARI tribe who Inhaled the powder without the assistance of 
another man, snuffing the EPENA by himself from his open hand, was the only one whose "dances" 
differed from the general manner : 

(1) The phases of his "dance" lasted not more than 15 minutes, (2) In the Intervals of his 
"dance" he inhaled some further doses of EPfiNA. He was the only one we saw snuffing during 
the Intoxicating state and not only hefore It. 
It Is possible that In his case the Initial doses, Inhaled without the powerful blow of another man, 
had not provoked the common intoxicating effect. So he was forced to snuff again. 




Fig. 14.— The "dance" under the effect of "EPENA." 



331 




Fig. 15. — . . . turned himself with high lifted arms to the mountain-range. 

been able to threaten to throw a poisoned arrow at me, if I had not disap- 
peared. My interpreter, who liad understood these words — in contrast to 
me — had hastened to fetch me back to the hut and translated the threat. 

The "dances", the movements of the arms in the normal intoxication 
state — as such it could be said — were very different from those seen on our 
first expedition, in the few minutes when the two young men were dancing 
on the square under the effect of the other snuff powder, mentioned in foot- 
note 1. These Indians doubtless had lost consciousness. 



332 




Fig. 1 6. — Typical face expression during the intoxication. 



333 



We talked with a young Indian of the KAUARETARI-tribe who had 
learned Portuguese in the mission-school in Tapuruquara. We gathered some 
explanations about the ceremony from this conversation : 

We asked, "Do you snuff EPfiNA?" He answered, "No, I am not allowed 
to. I am not grown up yet !" 

"When will you grow up ?", we then asked. 

"I don't know", he said, "but I think it will be soon." 

Next question : "Who decides when you are grown up ? " 

"My father. He shows me how to make the EPfiNA powder, and tells me 
what happens when I sniff it." 

Question : "What will happen then?" 

Answer : "Then I will see the HAKULA, who are big men living there 
above in big huts." — He pointed to the sky and continued : "The EPfiNA 
makes me so big that I can see them and talk with them !" 

Another Indian named Daniel, who had lived in the Tapuruquara-mission 
for some years before returning to the tribe and marrying, told me that he 
had seen " ANGELS" while under the effect of the EPfiNA. And that 
he had talked with them ! 

This one Indian tells us that he will see "big men". Another says that he 
saw "angels". This shows that the EPfiNA has two effects : 

First : The real effect well-known from the experiments of Doctor Becher 
and Doctor Richard E. Schultes. The Indian feels that he is a giant; every- 
thing around him takes enormous and magnificant forms. In the midst of 
a super-dimensional world, he feels like a superman ! Consequently his move- 
ments correspond to this state of excitation. These are braggart's gestures. 
These symptoms are accompanied by profuse salivation, a bad headache, a 
fixed stare and heavy perspiration. The symptoms reveal a state of strong 
intoxication. 

The second effect is imagined. The Indian sees things he has been taught 
to see. One sees "big men" because his father has told him that he Avould. The 
other saw "angels" because he had been taught in the mission that they are 
more powerful than HAKULA-spirits ! 

It can "be assumed that these Indians think about the HAKULA spirits 
and want to speak with them to cure a sickness or succeed in hunting. But 
my general impression is that many Indians take snuff only for kicks — to 
experience a bigger world. 

After about an hour, the effects of the snuff diminish. The dancer slows, and 
goes to his hut to lie down in his hammock, where he apparently falls asleep. 
Several Indians who had taken snuff and danced early in the afternoon, were 
seen in the evening at about eight o'clock seated around the fire as if nothing 
had happened. The duration of the snuff effects is comparatively short. One 
of our interpreters said to me that they don't like to take snuff in the evening 
because they can't sleep afterward. We can conclude from this that perhaps 
the apparent sleep in the hammock after the dance is not . really sleep but 
exhaustion, or the need to rest an aching head. 

It is certain, however, that the violent headaches and nausea are caused 
by the way that the snuff is taken — blown into the nostrils — that the head- 



334 



ache is temporarily relieved by the drug. Otherwise, the Indian would not 
be able to behave so violently in the square. After about an hour, the exilarat- 
ing, euphoric effect of the snuff backfires and turns into a hangover. 

The "Parica" of the Tucano-Medicine Man Agostino 

Most of the Indians who live in the village of Tapuruquara on the Upper 
Eio Negro are TUCANOS, who abandoned their old tribe territory on the 
PAPURf River. Agostino is the "Page", the medicine man, in this village, 
and he still uses "PARICA", a snuff that he prepared in our presence. He 
uses the same raw-material as the WAIKA Indians — ^the inner layer of the 
bark from VIROLA CALOPHYLLOIDEA, Markgraf , but he prepared 
the powder in a very different manner. 

With his knife he scraped off the inner layer of the bark moistened by the 
red-brown liquid. Then he threw these scrapings into a pot partly filled with 
water. In this water they were thoroughly kneaded, and squeezed so that 
the water turned muddy and took a reddish-brown colour. Then this muddy 
liquid was set to evaporate over a slow fire. 




Fig. 17. — The reddish-brown liquid was set to evaporate over a slow fire. 



335 



"It should not boil very rapidly", explained Agostino. And, indeed, three 
hours passed before the quart of liquid had become a hard, dark crust on the 
bottom of the bowl. From time to time a dirty foam rose to the surface, and 
the "Page" Agostino removed it with a little branch. Also, other impurities 
like fibres of the bark rose up with the bubbling and were eliminated in the 
same way. Finally nothing remained except a thick, dark brown syrup with 
a strong smell. Now, Agostino lowered the fire still more. The final drying 
was done very slowly, probably to prevent burning. 

The residue was a hard crust that was scraped off with a knife. It was the 
concentrate of that red-brown liquid that had begun to exude from the inner 
side of the bark, as well as from the trunk of VIKOLA CALOPHYLLOI- 
DEA, Markgraf. The scraped residue was ground into a fine powder with 
a smooth stone. 

With this process the "parica" was ready as Agostino said. It was not 
mixed with ashes or other ingredients. He explained that he, the medicine 
man, is the only one allowed to inhale the snuff powder. 

We didn't see the intoxicating effect, here, but it was confirmed by inhabi- 
tants of the village that it is very strong. Therefore Agostino can snuff his 
"PARICA" only twice a month at the most. He inhales the "PARICA", as 
he told us, before diagnosing the trouble with his patients. In the intoxicated 
state he stammers confused words which are interpreted by his brother. Later 
on he tries to cure the patient, using for the treatment the rattle "NASH 
SA" and the quartz crystal "MARIA PIRI". 




Fig. 18. — Finally nothing remained except a thick, dark-brown syrup. 



336 



Fig. 19. — The residue was ground into a fine powder with a smooth stone. 



BIBLIOGRAPHY 

Bechlek, H. "Die Surira and Pakidai, zwei Yanonami-Stamme in Nordwestbrasilien." 

Hamburg, Cram, De Gruyter & Co. 1960, 133 pp. 
HoLMSTEDT, B. "Tryptamine Derivatives in Bpena, An Intoxicating Snuff used by some 

South American Indian Tribes." Arch. int. Pharmacodyn. 156 : 2, p. 285-305. 1965 
KocH-GRiJNBERG, Th. "Vom Roroima zum Orinoco, Erletnissc ciner Reise in Nord- 

brasilien und Venezuela 1911-1913," Stgt. Band III (1923 ) 386 pp. 
SCHULTES, R. E. "A new narcotic snuff from the Northwest Amazon." Bot. Museum 

Leaflets, Harvard Univ. 16 (1954), 297-316. 
ScHULTES, R. E. "Ethnobotanili amerikanischer Halluzinogene," Planta Medica, 13. 

Jahrgang, Heft 2, Mai 1965, Hippokrates, Stgt. 
Seitz, G. J. People of the rain forest, Heinemanu, London, 1962 

Wassen, S. H. "The Use of Some Specific Kinds of South American Indian Snuff and 
Related Paraphernalia," Etnologiska Studier, vol. 28, G<5teborg 1965 

Wassen, S. H., and Holmstedt, B. "The use of parica, an ethnological and pharmaco- 
logical review," Bthnos 28, 5-45, 1963 

Zeeries, O. "Medizinmannwesen und Geisterglauben der Waika-Indianer des Oberen 
Orinoco," Ethnologica 2, Koln, E. I. Bill ( 1960) , 487-507. 



337 



Zeeries, O. "Waika, Die kulturgeschichtliche Stellung der Waika-Indianer der Oberen 
Orinoco in Rahmen der Volkerkunde Siidamerikas." 1964. Klaus Renner Verlag, Mtln- 
clien (Ergebnisse der Frobenius-Expedition 1954/55 nacli Slidost-Venezuela. Band I. 
Waika. ) 



338 



Chemical Constituents and Pharma- 



Bo HOLMSTEDT AND JaN-ErIK LiNDGREN 

Department of Toxicology, Swedish Medical Research Council 
Karolinska Institutet, Stockholm, Sweden 

About ten years ago E. C. Homing and co-workers isolated from seeds of 
Piptadenia peregrina^ a leguminous plant, indole alkaloids which were identi- 
fied by means of paper chromatography, colour reactions, fluorescence and 
infrared spectra (Stromberg 1954, Fish, Johnson and Horning 1955). They 
found the seeds to contain dimethyltryptamine-A'-oxide (DHT-A-^-oxide) 
and Bufotenine (5-OH-DMT) and its corresponding N-oxide. The seeds of 
Piptadenia peregrina is the most commonly known botanical source of snuffs 
made by South American Indian tribes, and is inhaled to produce visions and 
hallucinations. The interest of Homing and co-workers arose from the prop- 
erties of the crude drug. As a result of these analyses synthetic dimethyl- 
tryptamine (DMT) has come to be used experimentally by psychiatrists, in 
order to produce shortlasting states of illusions and hallucinations (Szara 
et al. 1957, 1961, Boszormenyi and Grunecker 1957) . 

Ethnological and botanical evidence in recent years demonstrates clearly 
that Piptadenia peregrina by no means is the main constituent of all snuffs 
used by South American Indians. In view of this it was felt necessary to make 
a general investigation of whatever material of this kind that could be col- 
lected. The first results of these studies are reported here. Modern techniques 
of analysis such as gas chromatography and the combination of gas chroma- 
tography and mass spectrometry (Ryhage 1964) offer possibilities for an 
accurate analysis even of very small amounts of material, such as can usually 
be obtained from museum specimens. 



Ethnological and botanical specimens 

Ep^na snuff collected in 1965 at Rio Marauia. Ep4na snuff collected in 1965 at Rio 
Maturaca. Snuff prepared by Pag6 Agostino collected in 1965 in Tapuruquara. All were 
obtained from Mr. Georg J. Seitz, Caixa Postal 2605, Rio de .Taneiro. 

Paricd obtained from Dr. Stig Ryd6n at the Ethnographical Museum in Stockholm. 

*This investigation was supported by Grant MH-12007 from the National Institute 
of Mental Health, U.S. Public Health Service, Chevy Chase, Md. 




South American Snuffs 



Material and methods 



List of abieviations used 

DMT =Af,A^-Dimethyltryptamine 

MMT =7V^-Monomethyltryptamine 

5-MeO-DMT=5-Methoxy-2V,Af-dimethyltryptamine 

5-MeO-MMT=5-Methoxy-2V^-monomethyltryptamine 

5-OH-DMT =5-Hydroxy-2V,2V-dimethyltryptamine (bufotenine) 

GLC =Gas-liquid-chromatography 

MS =Mass spectrometry 



339 



The specimen was collected In 1955 by the late Gustav Bolinder among the Piaroa Indians 
(Orinoco region, Venezuela). Sample No. 56-7-282 Statens Etnografiska Museum, 
Stockholm. 

Yopo snuff, obtained from Mr. Donald Overton, School of Tropical and Preventive 
Medicine, College of Medical Evangelists, Dept. of Biotoxicology, Loma Linda, Calif., 
collected in Colombia 1956. Sample No. P56-70-11. 

Epena snuff, obtained from Dr. H. Becher, Niedersachsisches Landesmuseum, Abteilung 
fiir Volkerkunde, Hannover, collected among the Surara Indians in 1956. 

Seeds from Piptadeniw peregrina, obtained from the Abbott Laboratories, collected 
in 1948 in San Juan, Puerto Rico, Sample No. (N-2003-C) . 

Seeds from Piptadenia peregrina, obtained from Dr. W. Haberland, Museum fiir 
Volkerkunde, Hamburg, collected by Dr. Franz Caspar among the Tupari Indians 
(Caspar 1953). 

Bark from Piptadenia peregrina, obtained from Mr. Donald Overton, collected in 
Colombia 1956. Sample No. P56-70-7. 

Bark from Virola calophylla, obtained from Mr. William A. Rodrigues, Manaus, Brazil, 
1964. 

Material used in gas chromatography — mass spectrometry 

Gas Chrom P 100-120 mesh, Applied Science Lab., State College, Pa., U.S.A. F-60 (a 
methyl p-dichlorophenylsiloxane polymer, Dow Corning, Midland, Mich., U.S.A.). 
EGSS-Z ( = Z a copolymer from ethylene glycol, succinic acid and methyl phenyl siloxane 
monomers. Applied Science Lab.). SE-30 silicone, Applied Science Lab. PDEAS (phenyl- 
diethanolamine succinate, Wilkins Instrument & Research, Walnut Creek, Cal., U.S.A.). 

Dichlorodimethylsilane, Hopkins & Williams Ltd., Essex, England. 

Reference compounds and reagents 

5-Methoxy-N,N-dimethyltryptamine, 5-methoxy-N-monomethyltryptamine, N-mono- 
methyltryptamlne bioxalate were kindly placed at our disposal by Dr. A. Hofmann, 
Sandoz A.G., Basle. Harmine and tetrahydroharmine hydrochloride were kindly placed 
at our disposal by Dr. K. Bernauer, F. Hoffmann-La Roche & Co., A.G. Basle. N,If-J)\- 
methyltryptamine (Aldrich Chemical Co., Inc., Milwaukee, Wis., U.S.A.). Harmine 
(Fluka A.G. Buchs SG, Switzerland). Bufotenine was prepared from Piptadenia pere- 
grina by E. C. Horning, Baylor University, College of Medicine, Texas Medical Center, 
Houston, Texas, U.S.A. All other reagents used were of "reagent grade" and from differ- 
ent manufacturers. 

Isolation of organic bases 

5-20 g of the powdered material was treated according to a procedure known to be 
satisfactory for phenolic amines in the indole series (Fish, Johnson and Horning 
1955). The isolation procedure was followed in detail but the amounts of solvents were 
reduced with respect to the initial weight of the sample. 

The steps of isolation procedure were followed by tests using Ehrlich's reagent. 
After drying with magnesium sulphate the final product was obtained upon removal 
of the solvent. The total alkaloids obtained were then dissolved either in methanol or 
in tetrahydrofurane. 

Oas chromatography (GLG) 

Gas chromatographic analysis was performed with an F & M Model 400 apparatus 
equipped with a hydrogen flame ionization detection system. 

The column support, 100-120 mesh Gas Chrom P, was acid washed and silanized 
according to the method described by Horning et al. (1963). The coating was applied 
by the filtration technique (Horning, et al. 1959, 1963). The stationary phases used 
were (1) 6% F-60 and 2% EGSS-Z (2.25 m x 3.2 mm glass tube), (2) 5% SE-30 
(4 m X 3.2 mm glass tube). The F-60-Z column was operated at 190° and the SE-30 
column at 210°. The fiash heater and detector cell were kept 30-40° above the column 
temperature. The flow rate of the carrier gas, nitrogen, was 60 ml/min. Samples were 
injected in methanol or tetrahydrofuran solution with a Hamilton syringe. 



340 



Gas chromatography-mass spectrometry (0LC-M8) 

The principles of the technique have been described in detail by Ryhage (1964). The 
mass spectrometry work was carried out with LKB 9000 gas chromatograph-mass spec- 
trometer including a fast scan system and the Ryhage "molecule separator." The ion 
source was 270°, the electron energy was 70 eV and the electron ionization current 60aiA, 
respectively. The separations were made on systems consisting of 3% PDEAS at 190° 
or 5% SE-30 at 200°. The column consisted of a 2 m x 3.2 mm glass tube. Helium was 
used as the carrier gas. At the outlet of the column, the separated compounds were con- 
centrated and continuously fed into the mass spectrometer. The mass spectrometer 
simultaneously serves as a gas chromatographic detector and for recording of mass 
spectra of the compound as they emerge from the column. The reference compounds 
were run through the column, and the mass spectra of the compounds recorded. The 
alkaloid fractions prepared as described above, were then run under identical conditions, 
and mass spectra were recorded from the gas chromatographic x)eaks having the same 
retention times as those of the reference compounds. 

Results 

The results of the authors' analysis of crude drugs such as parica, epena, 
etc. and corresponding botanical specimens are contained in Fig. 1-14. In 
table 1-2 our own results as well as those of previous investigators have 
been included. In every case the peaks in the gas chromatograms have been 
corroborated by mass spectra obtained with the combination instrument. 
This method assures complete identity with the reference compounds, and 
gives direct evidence for identity in contrast to indirect methods such as 
relative retention times. 

Snuffs 

In all six snuffs were examined (Table 1). In the crude drugs we have 
identified the various tryptamines. In three of them 5-MeO-DMT was the 
main component. DMT was identified in five but was nowhere found to be 
the main component. 5-OH-DMT was found in substantial amounts in two 
snuffs. One drug proved to have as much Bufotenine as DMT. This snuff has 
very little 5-MeO-DMT but in addition to simple indoles also contains 
harmine. Only one drug has 5-OH-DMT as its main constituent but contained 
in addition DMT and 5-MeO-DMT. Two compounds hitherto unidentified in 
South American snuffs were found to be present namely MMT and 5-MeO- 
MMT. Only one snuff contained exclusively ^-carbolines. 

Plants 

As a comparison, plant material from Piptadenia peregrina and Virola 
calophylla were examined in identical ways. Piptadenia seeds from two 
various locations proved to contain in one case 5-OH-DMT and in another 
case 5-MeO-DMT as the main constituent. The bark from Piptadenia when 
examined contained the following substances: DMT, MMT, 5-MeO-DMT 
and 5-MeO-MMT where 5-MeO-DMT by far was present in the highest con- 
centration. Finally, the bark from Virola calophylla proved to contain DMT, 
MMT and 5-MeO-DMT, the highest concentration in this case being DMT. 



341 




• 






44 




1 PEAK 3 1 




■ 


160 






! 


173 20«' 



20 40 60 80 100 120 140 160 180 

m/e 



20 40 60 80 100 120 140 160 180 200 

m/e 



20 40 60 eO 100 120 140 160 180 200 

m/e 





20 40 60 80 100 120 140 160 180 

m/e 



20 40 60 80 100 120 140 160 180 200 

m/e 



20 40 60 80 100 120 140 160 180 200 

m/e 



Fig. 2. — Mass spectrometric recording of compound in peak effluents from alkaloid 
fraction (Fig. 1) and reference compounds. Conditions: Column 2 m; i.d. 3.2 mm; 
3% PDEAS; 100-120 mesh Gas Chrom P; temp. 190^ 



Fig. 1. — Gas chromatogram of alkaloid fraction from South American snuff prepared 
by Pag4 Agostino, obtained from Mr G. Seitz. Tucano Indians, Tapuruquara, 1965. 
GLC conditions: Column 2.25 mm; i.d. 3.2 mm; 6% F 60 and 2% EGSS— Z on 100- 
120 mesh Gas Chrom P; temp. 190°; flow 60 ml per min. Upper panel high magnifica- 
tion. Lower panel low magnification. Mass spectra recorded simultaneously from 
peak effluents of extract and model substances injected under similar conditions, see 
Fig. 2. 



343 



Fig. 3. — Gas chromatogram of alkaloid fraction of Epena snuff obtained from Mr G" 
Seitz. Waica Indians, Rio Marauid, 1965. GLC conditions: Same as for Fig. 1. Upper 
panel high magnification. Middle panel low magnification. Lower panel reference 
substance recorded simultaneously. Mass spectra from effluent from peak 2 and model 
substances injected under similar conditions, see Fig. 4. Mass spectrometric control 
of peak effluents: Peak 1 and DMT: Molecular ion at m/e 188; other peaks at m/e 
58 (base peak), 103, 115, 130, 143. Peak 3 and 5-MeO-DMT: Molecular ion at m/c 
218; other peaks at m/e 58 (base peak), 103, 117, 160, 173. 



344 



3 

I 



2 




OMT 

5-MtO-DMT 



S-M«0-MMT 

MMT 



1 




|5 20 30 AO 

MINUTES 

345 



262-016 0-67— 24 



Fig. 4. — ^Mass spectrometric recording of compound in peak effluent from peak 2 from 
alkaloid fraction (Fig. 3) and reference compound. Conditions: Same as for Fig. 2. 



346 



100 



90 - 



80 - 



if) 70 
c 

CD 
C 



60 



50 

> 



a> 



40 
30 
20 

10 



44 



PEAK 2 



130 



103 115 

jL, LL_ 



143 



174 



—I — " ' > " — n — ""-T" — ■ " I I' " r 

20 40 60 80 100 120 140 160 



m/e 



100 



90 



^ 80 
>> 

^ 60 
c 

(D 50 
> 

D 40 

CD 

30 



20 
10 



44 



MMT 



H 



130 



103 



115 



^1 llii LL, U 



143 174 



1 — " T • ' ' " i " — — T — - — r — ' " I r" r 

20 40 60 80 100 120 140 160 

m /e 



347 



Fig. 5. — Gas chromatogram of alkaloid fraction of Epena snuff obtained from Mr G. 
Seitz, Araraibo Indians, Rio Maturaca, 1965. GLC conditions: Same as for Fig. 1. 
Upper panel alkaloid fraction. Lower panel reference substances. Mass spectrometric 
control of peak effluents: Peak 1 and DMT: Molecular ion at m/e 188; other peaks 
at m/e 58 (base peak), 103, 115, 130, 143. Peak 2 and 5-MeO-DMT: Molecular ion 
at m/e 218; other peaks at m/e 58 (base peak), 103, 117, 160, 173. 



348 



«4 




349 



I 



I 



• I 

1 1 



\ 



4 



5-MeO-DMT 



HARMINE 



DMT 



5-OH-DMT 



I I J— 

10 20 30 

MINUTES 

350 





20 40 60 80 100 120 140 160 180 200 

m/e 



20 40 60 80 100 120 140 160 180 200 

m/e 



58 



5-OH-OMT 



103 



117 146 204 



20 40 60 80 100 120 140 ISO 180 200 

m/e 





100 r 




90 ■ 




80 ■ 








70 - 






c 
a< 


60 - 


c 






50 ■ 


a; 




> 






40 ■ 


D 








30 • 



20 

10 



HARMINE 
chjO-CXn 

H CH, 



212 



169 



106 



197 



20 40 60 80 100 120 140 160 

m/e 



eo 200 



Fig. 7. — Mass spectrometric recording of compound in effluents from peak 3 and 4 from 
alkaloid fraction (Fig. 6) and reference compounds. Conditions: Column 2 m; i.d. 3.2 
mm; 5% SE-30; 100-120 mesh Gas Chrom P; temp. 200°. 



Fig. 6. — Gas chromatogram of alkaloid fraction from Parica obtained from the Ethno- 
graphical Museum, Stockholm, collected by the late Prof. Bolinder. Piaroa Indians, 
Venezuela, 1955. Column 4m; i.d. 3.2 mm; 5% SE-30 on 100-120 mesh Gas Chrom P; 
temp. 210°; flow 60 ml per min. Upper panel alkaloid fraction. Lower panel reference 
substances. Mass spectrometric control of peak effluents: Peak 1 and DMT: Molecular 
ion at m/e 188; other peaks at m/e 58 (base peak), 103, 115, 130, 143. Peak 2 and 5- 
MeO-DMT: Molecular ion at m/e 218; other peaks at m/e 58 (base peak), 103, 117, 160, 
173. Mass spectra from effluents from peak 3 and 4 and model substances, see Fig. 7. 



351 



Fig. 8. — Gas chromatogram of alkaloid fraction from Yopo, Colombia, 1956, obtained 
from Mr Donald Overton. Sample number P56-70-11. GLC conditions: Same as for 
Fig. 6. Upper panel alkaloid fraction. Lower panel reference substances. Mass spectro- 
metric control of peak effluents: Peak 1 and DMT: Molecular ion at m/e 188; other 
peaks at m/e 58 (base peak), 103, 115, 130, 143. Peak 2 and 5-MeO-DMT: Molecular 
ion at m/e 58 (base peak), 103, 117, 160, 173. Peak 3 and 5-OH-DMT: Molecular ion 
at m/e 204; other peaks at m/e 58 (base peak), 103, 117, 146, 159. 



352 



3 

I 



5-MeO-DMT 



DMT 



5-OH-DMT 



r 

10 

MINUTES 



20 



353 



Fig. 9. — Gas chromatogram of alkaloid fraction from Epena snuff obtained from Dr H 
Becher. Surdra Indians 1956. GLC conditions: Same as for Fig. 6. Upper panel alkaloid 
fraction. Lower panel reference substances. Mass spectra recorded simultaneously from 
peak effluents of extract and model substances injected under similar conditions, see 
Fig. 10. 



354 




HARMINE 

I 

HARMALINE 



TETRAHYDROHARMINE 



10 20 30 

MINUTES 



> 40 - 



"55 30 - 
20 - 
10 - 



PEAK I 



f72|87 



KM 



i», ^ HI ill ii 



201 



216 



BO 100 120 140 ISO i80 200 

m/e 






no 




90 




80 








70 






c 


60 








50 


a; 




> 


40 


o 




a> 


30 


DC 



TETR AH YDROHARM I NE 



" CM, 



201 



172 187 



m 



-I — T— 



a. > «ll 1 1 



216 



i 



20 40 60 80 100 120 140 iSO ISO 2CX) 

m/e 





100 




90 




80 








70 


"55 




c 


60 








50 






> 






40 


O 








30 




20 



10 - 



HARMINE 



CK, 



212 



169 



106 



197 



2040 60 80 OO BO t40 tec e: SCO 

m/e 



Fig. 10. — Mass spectrometric recording of compounds in peak effluents from alkaloid 
fraction (Fig. 9) and reference compoimds. Conditions: Same as for Fig. 7. 



>• 

Fig. 11. — Gas ckromatograpliie comparison of alkaloid fraction in Piptadenia seeds 
obtained from various locations with reference substances. Upper panel seeds of Pipta- 
denia peregriua obtained from Abbott Xo. X-2003-C, Puerto Rico 1948. Pre\"iously 
analysed by Homing et al. 1955. Main constituent 5-OH-DMT. Middle panel seed of 
Piptadenia peregrina collected by F. Caspar. Tupari Indians, Ptio Branco, Brazil, 1953. 
Main constituent 5-MeO-DMT. Lower panel reference substances, ilass spectro- 
metric control of peak effluents: Upper panel — Left peak and DMT: ]\Iolecular ion at 
m/e 188; other peaks at m/e 58 (base peak), 103, 115, 130, 143. Right peak and 5-OH- 
DMT: [Molecular ion at m/e 204; other peaks at m/e 58 (base peak), 103, 117, 146, 159. 
Middle panel — Left peak and D]\IT: Molecular ion at m/e 188; other peaks at m e 58 
(base peak), 103, 115, 130, 143. Right peak and 5-MeO-DMT: Molecular ion at m/, 
218; other peaks at m/e 58 (base peak), 103, 117, 160, 173. 



356 




357 




2040«o SO ooeoMoeoiao 





[PC*K 2 1 

44 




ISO 






oa IS 

1 ■ ■ 


rts itV 


20 *t 


60 BO OO so 

m/e 


MO CO 



100 
90 






OMT ^. 

OP---'-: 


100 
90 




44 




»* 00 




SB 


>! BO 




yyT 




1 eo 






s 

|eo 






u SO 
O 40 






^ 90 
O 40 




ISO 




(t 50 






(t » 
20 








?0 

10 




^119 oo|*' ite 


10 


— ^ 


i.ii..r^ 


143 174' 







44 








S-M*0-WWT 














KO 








IIS 



20 40 eo eo I 



20 40 eo BO 100 120 140 GO IBO 200 



Fig. 13. — Mass spectrometric recording of compounds in peak effluents from alkaloid 
fraction in Fig. 12 and reference compounds. Conditions: Same as for Fig. 2. 



Fig. 12. — Gas chromatogram of alkaloid fraction from bark of Piptadenia peregrina 
obtained from Mr. Donald Overton, collected in Colombia. 1956. Sample number 
P56-70-7. Column conditions: Same as for Fig. 1. Upper panel high magnification. 
Middle panel low magnification. Lower panel reference substances. Mass spectra 
recorded simultaneously from peak effluent of extract and model substances injected 
under similar conditions, see Fig. 13. 



359 



I 

I 




I MINUTES 

Fig. 14. — Gas chromatogram of alkaloid fraction from bark of Virola calophyUa. JSIanaus 
1964. GLC conditions: Same as for Fig. 1. Upper panel alkaloid fraction. Lower panel 
reference substances. Mass spectrometric control of peak effluents: Peak 1 and DAIT: 
Molecular ion at m/e 188; other peaks at m/e 58 (base peak), 103, 115, 130, 143. Peak 
2 and MMT: Molecular ion at m/e 174; other peaks at m/e 44 (base peak), 103, 115, 
130, 131, 143. Peak 3 and 5-MeO-DMT: Molecular ion at m/e 218. other peaks at m/e 
58 (base peak), 103, 117, 160, 173. 



360 



Table 1. — Distribution of indole alkaloids in South American snuffs 



Name 


Origin 


Alkaloid 


Reference 


Paric^ 


Venezuela 


5-OH-DMT 


Fish and Horning 
1956 


Parica 


Colombia 


5-OH-DMT 




Ep^na 


Waica Indians 


DMT 

5-OH-DMT 
5-MeO-DMT 


Holmstedt et al. 1964 


Ep^na 


Yanonami Indians 


DMT 

DMT-N-oxide 

5-OH-DMT 

5-OH-DMT-N-OAide 


Marini-Bettolo et 
al. 1964 


Epena 


Surara Indians 


Harmine 

Tetrahydroharmine 


Bernauer 1964 


Parica 


Tucano Indians 


Harmine 

Harmaline 

Tetrahydroharmine 


Biocca et al. 1964 


Epena 


Tucano Indians 


DMT 

5-MeO-DMT 
5-MeO-MMT 


Present investigation 


Ep^na 


Waica Indians 


DMT 
MMT 

5-MeO-DMT 




Epdna 


Araraibo Indians 


DMT 

5-MeO-DMT 




Yopo 


Colombia 


DMT 

5-OH-DMT 
5-MeO-DMT 




Parica 


Piaroa Indians 


DMT 

5-OH-DMT 

5-MeO-DMT 

Harmine 




Ep6na 


Surara Indians 


Harmine 

Tetrahydroharmine 





262-016 0-67— 25 



361 



Table 2. — Distribution of indole alkaloids in South American plants used for 

snuff preparation 



Plant 


Part 


Origin 






Piptadenia 


Seeds 


Puerto Rico 


5-OH-DMT 


Stromberg 1954 


peregrina Benth. 










Piptadenia 


Pods 


Puerto Rico 


DMT 


Fish, Johnson, 


peregrina Benth. 




and 




and Horning 




Seeds 


Brazil 


DMT-N-oxide 


1955 








5-OH-DMT 










5-OH-DMT-N- 










oxide 




Piptadenia 


Seeds 


Puerto Rico 


DMT 


Present investi- 


peregrina Benth. 






5-OH-DMT 


gation 




Seeds 


Rio Branco 


DMT 








region, 


5-MeO-DMT 








West 










Brazil 






Piptadenia 


Bark 


Brazil 


MMT 


Legler and 


peregrina Benth. 






5-MeO-DMT 


Tschesche 1963 








5-MeO-MMT 




Piptadenia 


Bark 


Colombia 


DMT 


Present investi- 


peregrina Benth. 






MMT 


gation 








5-MeO-DMT 










5-MeO-MMT 




Piptadenia 


Pods 


Brazil 


DMT 


Fish, Johnson, 


macrocarpa 


Seeds 




DMT-N-oxide 


and Horning 


Benth. 






5-OH-DMT 


1955 








5-OH-DMT-N- 










oxide 




Piptadenia 


Bark 


Argentine 


5-MeO-MMT 


lacobucci and 


macrocarpa 


Pods 




DMT 


Ruveda 1964 


Benth. 






5-OH-DMT 






Seeds 




DMT 










5-OH-DMT 










5-OH-DMT-N- 










oxide 




Piptadenia excelsa 


Pods 


Argentine 


DMT 




(Gris.) Lillo 


Seeds 




5-OH-DMT 










5-OH-DMT-N- 










oxide 




Piptadenia 


Seeds 


Brazil 


5-OH-DMT 


Pachter, Zacka- 


colubrina Benth. 








rias, and 










Riberio 1959 


Mimosa hostUis 


Root 


Brazil 


DMT 




Benth. 










Virola calophylla 


Bark 


Manaus 


DMT 


Present 






Brazil 


MMT 


investigation 








5-MeO-DMT 





362 



Discussion 



Mass spectrometric fragmentation of tryptamines 

In the past years the mass spectrometer has taken its place beside other 
methods in studies of natural products. The unique function of this instru- 
ment is to delineate the molecular size and composition of a compound; 
in many cases it can also provide information on the arrangement of atoms 
in the molecule. The classical application of mass spectrometry, one in which 
its precision is superior to that of any other method, is in determining the 
molecular weight of an unknown compound. More extensive deductions 
regarding structures of complex molecules may often be derived from careful 
examination of the entire mass spectrum of a compound. 

The combination of mass spectrometry and gas chromatography as invented 
by Ryhage (1964) is even more advantageous, because it combines the means 
of identification described above Avith the best method so far described for 
the separation of a series of compounds. 

In the instrument available (LKB 9000), a mass spectrometer is coupled 
to a gas liquid chromatography (GLC) column. As the compounds emerge 
from the column they are ionized in the ion source of the mass spectrometer 
and about 10% of the total ion current is used for continuous registration of 
the effluent. Two molecule separators are coupled in series between the 
column and the gas inlet line of the mass spectrometer. With this technique 
the sample-to-heliuni ratio is increased at least a hundred times. Less than 
one fig of material introduced into the column suffices for a good mass 
spectrum. GLC-MS has the great advantage not only to resolve various 
substituted and non-substituted tryptamines, but also to give accurate 
identification. It is conceivable that the nonspecificity of the most commonly 
used method spectrophotofluorometry has prevented the elucidation of other 
normally occurring compounds than serotonin and tryptamine, and that with 
the progress in GLC-MS additional biogenic amines of physiological and 
pharmacological importance may be found. No doubt, the combination of 
GLC and mass spectrometry will be one of the powerful tools used in 
biological research for years to come. 

According to Budzikiewics, Djerassi and Williams (1964) simple indoles 
have a characteristic fragmentation pattern. By analogy with this the 
psychotomimetic substance 5-MeO-DMT discovered by us in South American 
snuff would have the following fragmentation pattern. 




363 



Here the main cleavage occurs as follows : 



CH30 




^^^^^ 



CH2-pCH2 -N(CH3)2 



N 
H 



160' 58 



The ions m/e 160 and 58 are clearly seen in the mass spectrmn. If one CH3 
on N is replaced by H such as occurs in 5-MeO-lSIMT the corresponding ions 
occur at m/e 160 and 44. The latter ion is found as the base peak of the 
spectrum. If one CH3 on N are replaced by other groups such as acetyl in 
melatonine a corresponding ion is formed. 

On the other hand m/e 160 will change according to different substitution 
in the indole nucleus such as occurs in bufotenine (m/e = 146) . 
m/e 173 may represent 




N' "^N(CH,), 




or 



CH 





m/e 174 may represent 



H® 

For m/e 115, 116, 117 in the spectrum the origin is not known, but the presence 
of these peaks seems to confirm previous belief that they are a good qualitative 



CH, 



364 



indication of indoles. The mass spectra of 5-OH-DMT, 5-MeO-MMT and 
MMT when scrutinized confirm the fragmentation pattern proposed for 
5-MeO-DMT. 

Plants containing indoles 

The first indoles in plants were isolated in the beginning of this century 
(Saxton 1965). Since then the number has been steadily increasing. Good 
accounts of their occurrence are available (Hochstein and Paradies 1957, 
Stowe 1958, Cerletti 1960, Downing 1962, Poisson 1965, Saxton 1965 and 
Morimoto et al., 1965, 1966). Unsubstituted and 5-substituted indoles com- 
mand special interest with regard to pharmacological effects in two instances. 

Firstly there are reports of cases of a disease called "staggers" in sheep 
pastured largely on a perennial grass, Phalaris tuberosa L. (Gallagher et al. 
1964). Investigation of this and related species of Phalaris has led to the 
isolation of DMT, 5-MeO-DMT, 5-MeO-MMT and 5-OH-DMT (Wilkinson 
1958, Culvenor et al. 1964) . 

Secondly, the same tryptamines as presented in table 1-2 of this review 
occur in the snuffs used in South America for intoxicating purposes. From 
the tables it is evident that tryptamines both imsubstituted and substituted in 
the ring (5-OH- and 5-MeO-) occur, and that both secondary and tertiary 
amines are present. In addition to this some snuffs contain y8-carbolines, 
either in combination with the simple tryptamines or solely. In South Amer- 
ican botany y8-carbolines (harmine, harmaline and tetrahydroharmine) are 
usually associated with the species of Banisteriopsis, wherefore it is very 
likely that this is their origin in the snuffs. Very likely this is an admixture 
to the snuff, although definite botanical proof for it is lacking at the moment. 
To the knowledge of the authors, simple indoles and ;8-carbolines have not 
yet been isolated from the same plant. 

The occurrence of both tryptamines and y8-carbolines in the South Ameri- 
can snuffs is pharmacologically interesting. The ^-carbolines are monoamine- 
oxidase inhibitors (Udenfriend et al. 1958), and could potentiate the action 
of the simple indoles. The combination of /8-carbolines and tryptamines would 
thus be advantageous. However, pharmacological actions of the y8-carbolines 
unrelated to monoamineoxidase inhibition has also been proven to exist 
(Schievelbein et al. 1966). Further botanical and chemical studies are obvi- 
ously needed to see if the two groups of compounds in the snuff are derived 
from one plant or a mixture of plants. 

Deposition and absorption of snuffs 

The equipment used for the administration of the powder in some cases 
consists of a straight tube equipped at one end with a palmkemel through 
which a hole has been bored. This end is fitted into the nostril of one person 
while another blows the powder forcefully through the opposite end of the 
tube. Another variation is a V-shaped tube, used for self-administration, 
where one end is put into the mouth and the other end into the nostril and the 
snuff is blown into the nasal cavity. Other equipment for the administration 



365 



exist among other tribes, the usual apparatus being the frequently described 
bifurcated tube (Safford 1916). This is used for administration by means of 
direct inhalation. 

The two means of administration, forceful blowing or inhalation can be 
expected to differ in the effect produced. It is necessary to consider here the 
broad features of normal nasal physiology. The stream of inspired air does 
not pursue a straight course from anterior nares to choana, but passes in a 
wide curve beginning at the nostril, extending through the olfactory fissure, 
and ending in the choana (Proetz 1953). The negative pressure produced in 
the nose on inspiration, reaches a maximum figure of 55 mm. of mercury. The 
air fluctuations are rarely of sufficient force or magnitude to carry foreign 
particles into the sinuses. During normal sniffing (inspiration) air is pro- 
jected against the nasal mucosa and the anterior portion of the nose, produc- 
ing eddies. Harrison (1964) let volunteers sniff pinches of barium sulphate 
powder up one nostril. Inspection revealed that in every case the powder 
collected primarily in the middle meatus. By forceful blowing as with the 
straight and the V-shaped tube a more widespread deposition on the nasal 
mucosa may be expected, and some particles even reach the lungs (China- 
choti et al. 1957). However, we must assume that the main part of the ad- 
ministered material affects the brain from the nose. From a theoretical point 
of view several possibilities exist. 

(a) The tryptamines reach the brain, via absorption from the richly vas- 
cularized nasal mucosa into the blood stream. It is well known that many 
other drugs have a very rapid action when applied in this way. 

(b) The compounds act directly on the brain without having been trans- 
ported through the general circulation. 

Anatomical reasons have been proposed for the direct action on the CNS 
of certain drugs, such as cocaine, through the nasal mucosa (Lewin 1927). 
The following veins communicate directly with the cranial cavity, the con- 
comitant veins of the arteriae ethmoidales, and a vein which accompanies a 
ramification of the anterior ethmoidal artery. The last one is an important 
connection between the nose and the cranial cavity. This vein accompanies 
the artery through the ethmoidale plate and makes connection within the 
cranial cavity, either with the network of veins of Tractus olfactorius or 
directly with a bigger vein in the orbital lobe. All the vessels mentioned are 
accompanied by lymph vessels, and it is conceivable that drugs can act 
directly on the brain without having to be transported through the general 
circulation. Experimental proofs for this are, however, lacking. 

Several observers have described the passage of simple solutions from the 
nose into the cranial cavity. (For references see Yoffey and Drinker 1938). 
Clark (1929), for example, stated that a solution of potassium ferrocyanide 
and iron ammonium citrate, dropped into the nasal cavities of rabbits, 
reaches the surface of the brain within one hour ( Sic ! ) . He believed that 
there was a pathway along "the perineural sheaths of the olfactory nerves". 
The existence of a current running centripetally in these perineural sheath 
spaces of the olfactory nerves under normal conditions was postulated. Faber 
(1937), came to similar conclusions as a result of experiments on rabbits. 



366 



In the series of experiments by Yoff ey and Drinker ( 1938 ) , this was definitely 
not the case. The results were of especial interest since by cannulation of 
the cervical lympli duct it was possible to show that dye was present in the 
lymph in high concentration over many hours, and yet could never be detected 
in the interior of the cranium. 

It seems evident that for anything but solutions of simple crystalloids, 
the cribriform plate offers an effective barrier to the passage of substance 
(non-living) from the nose to the interior of the skull. The rapidity of action 
of the tryptamines (minutes) also speaks against a direct transport from the 
nasal to the subarachnoidal cavity via the lymph vessels. 

Symptomatology 

The first written account of the action of the American intoxicating snuffs 
is that by Friar Kamon Pane on cohoba, published first in 1511 and quoted in 
detail by Wassen (this volume). Ramon Pane's observation of symptoms is 
revealing : 

... he takes a certain powder called cohoba, snufiBng it up his nose, which 
intoxicated them so that they do not know what they do and in this condition they 
speak many things incoherently in which they say they are talking with the cemis 
and that by them they are informed how the sickness came upon him. Having 
snuffed cohoba into their nostrils (so they call the intoxicating plant by which 
the bovites also are thrown into a frenzy), they say that the house is turned upside 
down the roofs and floors being interchanged and that men walk with their feet 
upward. Such is the strength of the powder of cohoba that it takes away the senses 
of using it. When the stupefaction begins to go away, he hangs down his head 
and clasps his knees with his arms. He remains in this state of suspended animation 
for a little while ; then he raises his head as one awakening from sleep and casting 
his eyes up at the sky at first he mutters a few rambling words to himself. The 
words which they say, none of our people understand. With this powder they 
lose consciousness and become like drunken men. 

This undoubtedly constitutes the first written account of the psychoto- 
mimetic effects of the tryptamines, and is astonishing in its correctness when 
compared to later descriptions only some of which will be quoted here. 
Ramon Pane's description also corresponds very well to what one can see 
in the film about the use of the epena among the Waicas made by Mr. Georg 
Seitz. Later explorers have, however, pointed out additional effects. Nimuen- 
daju (1948), (quoted from Wassen 1965) says: 

. . . the powder caused a general state of excitement and exaltation with 
auditory hallucinations, and a condition of feverish activity which ended with 
prostration or unconsciousness. According to Martius, individuals who were over- 
excited by the narcotic and suffocated, died on the spot. On the morning following 
"a narcotic spree'" the bodies of persons were often found shot with arrows or 
stabbed with knives. These murders were not considered as crimes and were blamed 
on the parica. 

Cohoba, according to Columbus, Ramon Pane, Las Casas and others who 
observed and reported its use in Haiti, was employed by the medicine-men 
chiefly to induce a state of trance ; more hedonistic uses have been described 
later (see Seitz this volume). The violent effect of this snuff indicated that 



367 



its chief ingredient was a powerful substance. None of the early commenta- 
tors on the custom says that the substance inhaled was derived from the 
tobacco plant, but before the close of the sixteenth century the snuff used in 
the cohoba ceremonies reported was assumed to be tobacco, and the associa- 
tion was continued up to our own time (Loven 1935) . Only a person entirely 
inexperienced in pharmacology and toxicology would, however, confuse 
the illusions and hallucinations described under the influence of cohoba, 
with a nicotine intoxication. The confusion of cohoba and tobacco was also 
largely dispelled by the paper by Safford ( 1916 ) . 

All modern evidence confirms the psychotomimetic action of the snuffs. 
Zerries (1964) and Seitz (this volume) describe how in the Waica tribe in- 
dividuals quickly become intoxicated by repeated inhalation of the snuff. 
The somatic symptoms are headache, salivation, vomiting, profuse perspira- 
tion, unsteady gait and a typical facial expression. During the intoxication 
the Indians are able to establish contact with the Hekula, the spirits of rocks 
and waterfalls in order to induce them to bring mishap and sickness to the 
enemies of the village. The medicine man becomes possessed by spirits, excited 
and sometimes loses consciousness. The best description of the use of epena 
is the one given by Becher (1960) relating details about the religious use of 
the compound, and how during the ritual the Lidians 'become so obsessed with 
the spirits that they have to be exorcised. Under the influence of the drug, 
the Indians identify themselves with the gigantic spirits of animals and 
plants Hekura (Hekula), and also have the impression that they personify 
themselves the Hekura (Surara tribe) . Becher, who became a member of this 
tribe, gives a rare description of his own experience when taking the snuff. 
His symptoms were the following (translation by the authors) : 

A few minutes (after taking the snuff) I felt terrible with a headache and 
nausea just as the boy who comes into contact with the drug for the first time. 
Shortly afterwards, I had a very strange experience, I felt myself to be a giant 
among giants. Everybody around me, people as well as dogs and parrots, seemed 
suddenly to have become giants. 

Interestingly enough this is a description of macroptic illusions. 

Dysmegalopsia^ synonymous with dysmetropsm^ is a disturbance of the 
visual appreciation of the size of objects which occurs with certain drugs. 
It can be subdivided into maeropsia and micropsia. These conditions may re- 
sult from disturbances in the peripheral motor perception, ?.e., eye muscles, 
but they also occur in toxic psychoses. Maeropsia has been described, par- 
ticularly in alcoholic delirium. Its most famous manifestation is the well 
known "pink elephants." It also occurs in intoxications with Amanita mus- 
caria (Kracheninnikov 1764) . The macroptic phenomenon has been treated in 
detail by di Gaspero (1908). It is interesting to know that these experiences 
are described by people who are fully oriented in time and space, and that 
during experience living persons and animals hut not dead ohjects, change 
size (compare Becher). The latter may be perceived in a different colour 
as to the giants. Maeropsia seems to be more common than micropsia, but 
the latter has been described as a result of intoxication with ether, alcohol, 
cocaine, chloral hydrate and cannabis (de Clerambault 1909). Apparently 



368 



it can occur also in intoxications with Banisteriopsis (Preuss 1921) . Beringer 
(1934), who has devoted a study to optic illusions and hallucinations, 
describes a third phenomenon, a change in size in one direction or the other 
somewhat reminiscent of what can be achieved with a modern zoom lens of 
a camera. 

Shortly after Horning et al. had isolated DMT and 5-OH-DMT from 
Piptadenia peregHna, Szara (1957), conducted experiments on himself with 
the injection of DMT. The symptoms he reported are in good agreement with 
what has been described by the explorers : 

In the third or fourth minute after the injection vegetative symptoms appeared, 
such as a tingling sensation, trembling, slight nausea, mydriasis, elevation of the 
blood pressure and increase of the pulse rate. At the same time eidetic phenomena, 
optical illusions, pseudohallucinations and later real hallucinations, appeared. The 
hallucinations consisted of moving, brilliantly coloured oriental motifs, and later 
I saw wonderful scenes, altering very rapidly. The faces of the people seemed to be 
masks. My emotional state was elevated sometimes up to euphoria. At the highest 
point, I had compulsive athetoid movement in my left hand. My consciousness was 
completely filled by hallucinations, and my attention was firmly bound to them; 
therefore I could not give an account of the events hapi)ening around me. After 
%-l hour the symptoms disappeared, and I was able to describe what had happened. 

Macropsia is also a frequent phenomenon in experimental DMT-intoxica- 
tions (Isbell, personal communication) . 

The action of 5-OH-DMT (bufotenine) is more controversial. Fabing and 
Hawkins (1956), reported that intravenous injection, over a three minute 
period, of 8 to 16 mg of bufotenine in human volunteers resulted in primary 
visual disturbances, alteration of time and space perception, and paresthesias. 
It is difficult to judge by this account whether any illusions and hallucina- 
tions really occurred. It seems that the observed phenomena can as well be 
interpreted as general somatic symptoms of intoxication. Neither Isbell nor 
Turner and Merlis (1959) themselves in their carefully conducted studies, 
could substantiate the claim that bufotenine injections had any effect on the 
central nervous system, whereas DMT under the same experimental condi- 
tions had psychotomimetic effects. 

Control experiments with various preparations of snuff have been carried 
out by two groups but have not proven the capability of the used prepara- 
tions to produce the intoxication attributed to it by natives or explorers. 
In a letter, Dr. Harris Isbell describes his experiment with the same com- 
pounds in the following way : 

We studied several forms of the material : Untreated snuff, roasted snuff, limed 
and roasted snuff, fermented snuff, fermented and limed snuff, fermented, limed 
and roasted snuff. Our subjects inhaled the snuff through straws. We obtained no 
reports that there were any subjective effects after inhalation of this material in 
amounts ranging up to 1 gram, and we further were unable to obtain any evidence 
of objective effects on pupillary size, tendon reflexes, body temperature, respiration, 
blood pressure etc., after doses ranging up to 1 gram orally. 

Inhalation of pure bufotenine in aerosol suspension, or oral ingestion of bufo- 
tenine in doses running up to 100 mg (total dose) also were without effect. 

The above quoted experiments were all performed with snuff made from 
the sample of Piptadenia peregrina in which Horning et al. had found 



369 



5-OH-DMT (bufotenine) to be the main component, and this fully explains 
the negative results. 

One measure of the ability of compounds to penetrate the nervous system 
is the lipid solubility, as determined by the lipid solvent-water partition 
coefficients. Gessner and Page (1962), found a low value for the chloroform- 
water partition coefficient of 5-OH-DMT, indicating a low lipid solubility 
attributable to the hydrophilic phenolic hydroxy group. Hence, the low 
activity of 5-OH-DMT could be related to its relative inability to cross 
the blood-brain barrier. The 5-MeO-DMT shown by the present investiga- 
tion to be the major component of most South American snuffs was, however, 
found to be a compound in which the right structure is present both for 
lipid solubility and central action. 

The animal experiments by Gessner and Page (1962) have pointed to the 
strong action of synthetic 5-MeO-DMT on the central nervous system, and 
its important role in the elucidation of central nervous mechanisms. The 
effect of 5-MeO-DMT on the conditioned avoidance response of trained rats 
was compared quantitatively, using a shuttle-box, with that of several other 
substituted tryptamines and LSD-25. At a dose level of 19 /^M/kg it had a 
pronounced effect on the conditioned avoidance response, much more pro- 
nounced than that due to DMT. A similar response was elicited by LSD-25 
at a dose level of 6 /xM/kg. 

Benington et al. (1965), report that the effect of 5-MeO-DMT on cat 
behaviour is dramatic. An intense sham rage response was induced within 
a few minutes. Of all drugs examined that induce sham rage in the cat, 
5-MeO-DMT is one of the most potent, and its potency was very close to 
that of LSD-25. From the rapid onset of the rage response induced by 
5-MeO-DMT by any route of administration, it is evident that the drug 
reaches the sites of action rapidly. The nature of the response suggests a 
central effect of a relatively short duration. 

It is outside the scope of the present investigation to go into the detailed 
effects of the various tryptamines with regard to their circulatory and other 
peripheral effects. (With regard to 5-MeO-MMT see Marczynski, 1959, 1960) . 
It ought to be mentioned, however, that the effects of 5-MeO-DMT on the 
general circulation are negligible compared to those of 5-OH-DMT (bufo- 
tenine). Detailed pharmacological and metabolic studies of 5-MeO-DMT 
are still lacking. No doubt its resemblance to serotonine, its solubility prop- 
erties, its relative lack of peripheral and marked central action of an obvious 
psychotomimetic nature will in the future make 5-MeO-DMT an important 
tool in psychopharmacological studies. Once again, one cannot but marvel 
at the ingenuity of the South American Indians who relentlessly seem to be 
able to find their way to the right herb containing the most active component. 

A cTcnow ledgermnt 

We thank Dr. R. Ryhage (Department of Mass Spectrometry, Karo- 
linska Institutet) for expert advice and laboratory facilities placed at oar 
disposal in connection with the recording of mass spectra. 



370 



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373 



Discussion on the Psychoactive Action 
of Various Tryptamine Derivatives 

Chairman — Bo Holmstedt 
Members of the Panel — JoiiN W. Daly 

Efren Carlos del Pozo 
Evan C. Horning 
Harris Isbell 
Stephen I. Szara 

Chairman Dr. Holmstedt: We have some questions from the audience, 
and I know that some of the participants are also prepared to elaborate upon 
what they have done themselves. 

Perhaps we should start with Dr. Szara, who had the courage to use 
dimethyltryptamine as an experimental tool for the first time, and we would 
be glad if he would give us a description of the symptoms he observed. 

Dr. Szara: I think the picture was very clear. We saw in Mr. Seitz's 
movie what the drugs can do, and how quickly ; so I would rather like to give 
a little summary of what we have done in the past twelve years with 
dimethyltryptamine, and how we came to start using it. Actually it was 
when I first read an article by Fish, Johnson and Horning in the Journal 
of American Chemical Society 77, 5892 (1955). These authors have found 
N,N-dimethyltryptamine, together with bufotenine, in snuff powder pre- 
pared by Haitian natives from Piptadenia peregrina seeds which the natives 
used in their religious ceremonies. The psychotropic effect was blamed on 
bufotenine, but it was unknown whether dimethyltryptamine was hallucino- 
genic or not. So I decided to synthesize it, and then tried it out on myself 
and other volunteers and friends who were courageous enough to volunteer. 
It was not active orally. I started taking this compound in very small quan- 
tities up to 250 mgs, but it was inactive. Then we started giving it intra- 
muscularly, doses of one mg/kg, Avhich give a very fast and very strong 
reaction. This resembled very closely symptoms which were described by 
Dr. Freedman the day before yesterday about LSD, so I would rather just 
summarize those symptoms which are similar to those of LSD, and point 
out some striking differences. 

The perceptual distortions are primarily visual in nature, and witli closed 
eyes you can see illusions and color patterns, primarily geometrical patterns, 
moving very fast, having sometimes very deep emotional content and 
connotation. 

There is an inability to keep attention focused on any outside task. It 
seems to be very difficult to maintain contact with reality, and this often 
leads to a panicky action. There is an enhanced dependence on the environ- 
ment for structure and for symbolic meanings, and increased association 
and search for synthesis, as Dr. Freedman mentioned. 



374 



There are some dissimilarities, however, when you compare the effects of 
dimethyltryptamine with those from LSD. The main difference is the rapid- 
ity of the onset and the shortness of the duration of action. After being given 
an injection intramuscularly, the symptoms begin in two or three minutes, 
and they last for only about thirty to forty-five minutes, or a maximum of 
an hour, and then it is just hangover and nothing else. The effects of LSD 
and mescaline last for four, six, eight and sometimes twelve hours, depend- 
ing on the dose and on the individual variations. 

Some other minor differences exist. In dimethyltryptamine there are more 
primary visual hallucinations, light flashes, colors, abstract forms and figures 
with oriental designs. There is a consistently larger but short-lasting auto- 
nomic effect, consisting of increased blood pressure and dilated pupils. The 
rapid onset of the strange experience and the overwhelming loss of control 
can cause panic reaction much faster than other known longer lasting 
hallucinogens. 

We have worked very extensively since this on the metabolism of dimethyl- 
tryptamine, and I don't know if now is the time to go into it. We have 
synthesized several compounds which are also hallucinogenic. They differ 
slightly in duration. They are slightly longer acting than dimethyltrypta- 
mine, and the autonomic reaction is slightly less. 

We were interested in the metabolism of this compound, and we have 
suggested that 6-hydroxylation may be a way of producing a psychoactive 
mc^^abolite. This has been questioned by Dr. Isbell and by some others, based 
on the work of 6-hydroxy-5-methoxydimethyltryptamine, which was sup- 
posedly metabolized and has been found inactive in the behavioral tests. 

I have repeatedly stressed in the last couple of years that our data strongly 
supports the notion that the 6-hydroxy pathway is somehow involved, 
although not necessarily through the first, and the main metabolite, which 
has been found to be the 6-hydroxydialkyltryptamine. The data on which 
we rely for this judgent are primarily clinical, obtained first on normal 
volunteers, later on alcoholic patients, in double blind tests. These studies 
have shown strong correlation between the rate of 6-hydroxylation and the 
hallucinogenic action as measured by rating scales and psychological reports. 

The other support for the role of 6-hydroxylation is the fact that if you 
prevent this pathway by substituting the 6-position by a fluorine, thus hav- 
ing a 6-fluorodiethyltryptamine, this compound has not been found to have 
hallucinogenic properties in patients. It does produce autonomic effects, 
pupillary changes, blood pressure changes ; but it does not produce the drift- 
ing away into a dream world and other phenomena characteristic for the 
hallucinatory activity. 

We have used these compounds mainly as tools in learning about the 
mechanism of action of this particular type of drug, in which there seems 
to be a very deep interest in psychiatry. 

Perhaps I could mention some experiments with tritium-labeled dimethyl- 
tryptamine, which illustrate very nicely how quickly this compound pene- 
trates the brain and reaches the area involved in the central nervous effec:ts. 



3Y5 



/ In one of the experiments we gave 10 mg/kg of DMT intraperitoneally 

to mice, the brain was taken out at various time intervals, and the small areas 
were analyzed by chromatography and scintillation spectrometry. In ten 
minutes you can get a maximum amount of unchanged DMT in the cortical 
areas, and slightly less in other areas which gradually subside, but some of 
the basic metabolites which contain the hydroxy lated metabolite have a 
slightly different course, and reach different areas of the brain later in time, 
but not in the first couple of minutes. 

This is just some of the data which we have not published yet, but we have 
done a lot of work combining these drugs with a precursor of serotonin, 
5-hydroxytryptophan. In these experiments there seems to be a very delicate 
regional change in the serotonin metabolism, primarily the hypothalamus 
area, when we give hallucinogenic diethyltryptamine, but not when we gave 
the nonhallucinogenic, 6-fluoro analog. 

We have published some of these data in the proceedings of a symposium 
on "Amines and Schizophrenia," (H. Himwich et. al.. Editors: Amines and 
Schizophrenia, Pergamon Press, Oxford, New York, 1966) . 

I would like to stop now. 

Chairman Dr. Holmstedt : Thank you. 

The thing which I personally would like to know from the two psychi- 
atrists on the panel is, what are the visual phenomena of these experimental 
patients? Do they have microptic and macroptic phenomena? Dr. Isbell. 

Dr. Isbell: Do they have micropsia and macropsia? Yes, they do, and 
the same individual may have both, in rapid or alternating fashion, and 
this may involve not only extraneous objects and people, but also his own 
body image. He may feel that he is nine feet tall, and then he may shrink to 
a point where he begins to get worried that he is going to get so small that 
he will completely disappear. The same alterations in size will occur in the 
environment. The room gets very small or very big, and simultaneously 
there are distortions of shape, color ; practically every kind of thing that you 
think of that would happen in the visual sphere does happen. 

Dr. Kline : Are these alterations in part emotional, or do you think they 
are totally physiological ? 

Dr. Isbell: I can't answer you. Dr. Kline. Things will happen in the 
same man at almost one time, and you can sometimes get from the patients 
themselves very interesting explanations why these things happened. 

Dr. Kline : Rinkle did some work with adrenolutin or adrenochrome in 
wliich the size of the person and the apparent distance from the observer 
was quite dependent, according to this report, on whether he liked the per- 
son or not. Some subjects even managed to see "through" certain people 
if they didn't like them. I have never heard any confirmation of this, and 
I was wondering whether it might not be an interesting subject for investi- 
gation. 

Dr. Isbell : I have personally never been able to correlate any particular 
subjective experiences that a given individual has with anything, except if 
one has observed him under drug on a previous occasion, it is very likely 
that the same type of phenomena will be seen on the second occasion. 



376 



I think that I might speak a little bit about some of the tryptamines other 
than dimethyltryptamine. One of these is bufotenine. It has been said that 
bufotenine is not a psychotomimetic drug. I don't think we should say that. 

The difficulty is that bufotenine is a drug that has extremely powerful 
and dangerous cardiovascular effects, and for that reason it is not possible 
to push the dose in man. Also, it would be difficult to differentiate whether 
psychotic reactions were due to central effects or to cardiovascular actions. 
Cardiovascular actions include hypertension and development of an arrhyth- 
mia which actually amounts to a ventricular standstill. The auricle does 
not beat, the beat drops out, and the ventricle takes over, and it is very 
frightening. Simultaneously with the hypertension and ventricular escapes, 
one sees spectacular cynanosis in the upper part of the body, similar to that 
which has been described in the carcinoid flush, which is presumably due 
to serotonin. So bufotenine is a difficult drug to work in man for this 
reason, and it would not be too surprising if it did not have some kind of 
a central action if it were possible to extract it out. 

G-Hydroxydimethyltryptamine had no effect in a dose of 1 mg/kg in 
our subjects, in fact. In contrast, my subjects had spectacular reactions to 
dimethyltryptamine. My men spoke of taking trips long before this term 
came into general use. They used to say that with dimethyltryptamine, "You 
can go to the moon and get back in time for breakfast" — so, they went to the 
moon long before the rockets landed. I hope they left a flag up there, but the 
6-liydroxy derivatives were without effect. The 5-methoxy congener, as Dr. 
Holmstedt said, has not been tested, and we are still awaiting animal 
pharmacology on it. 

I think we are, perhaps, forgetting that the psilocybin and psilocyn 
found in the mushroom are derivatives of tryptamine and serotonin with the 
hydroxyl group in the 4-position. These drugs give us the same kind of effect 
as does DMT. They are somewhat longer acting, and slower to start. 

One interesting thing is that the resemblance of the clinical phenomena 
one sees with dimethyltryptamine and LSD is very striking. If you get 
LSD daily you soon develop such a high grade of tolerance that one might 
as well be issuing water. Then, if you take people who are tolerant to LSD 
and test them with psilocybin and mescaline, you will find that they are 
markedly cross-tolerant. We were unable to show a high degree of cross- 
tolerance between dimethyltryptamine and LSD, so despite the similarity 
of chemical structure it may be that dimethyltryptamine and LSD may act 
by somewhat different mechanisms within the brain, although we cannot be 
sure of this. The only thing we can be sure of, is that there is no great degree 
cross-tolerance. 

Chairman Dr. Holmstedt: I can mention that as far as the animal ex- 
periments undertaken with the 5-methoxy compound are concerned, they 
have shown it to have a very weak effect on the circulation. My statement 
that bufotenine was not a psychotomimetic agent was based on two things : 
First your own work, Dr. Isbell ; secondly, that its solubility properties are 
such that it is not very likely to penetrate the blood-brain-barrier. 

37Y 

262^016 O — &7 26 



We have several questions. One is from Dr. Kline, and he wants to know 
whether all alkylated tryptamines are psychotomimetic. I don't think any- 
body can answer that fully. Dr. Szara did, however, try out a number of 
them. 

Dr. Szara : N,N-dibutyl- and N-monohexyltryptamines, which are higher 
homologues, were inactive in a few patients. There is no systematic study. 

Chairman Dr. Holmstedt : Another question : Can these states be termi- 
nated with phenothiazine derivatives, as is the case with LSD and mescaline ? 

Dr. Szara : We never had to terminate it, because it is so short acting, it 
is over before you realize it happens. 

Chairman Dr. Holmstedt : Question : "What ingredients in the snuff do 
you think caused the untoward side effects, based on similar experiments 
with purified chemical constituents?" 

The answer to that is that the tryptamines themselves may very well cause 
the side effects, as pointed out by Dr. Szara. 

Somebody also wants to ask Dr. Schultes a question: Why does he use 
the words "narcotic snuffs" or "hallucinogenic snuffs", and what is the dif- 
ference ? Do you want to answer that question. Dr. Schultes ? 

Dr. Schultes : There are any number of definitions of the word "narcotic". 
Having had a classical education, I use it as it was coined from the Greek, 
meaning any substance that benumbs the central nervous system, whether 
ever so slightly or producing a comatose state. There is no one good definition 
of the term. 

In this coimtry-, a substance is not a narcotic unless the Senate has declared 
it so. It has to be so declared under the Harrison Narcotics Act. For this 
reason, marijuana is not legally a narcotic. Then you have the popular and 
newspaper definition, meaning only the addictive and dangerous ones. Faced 
with this plethora of "definitions", I have decided to stay with the Greeks. 

Chairman Dr. Holmstedt : Thank you, Dr. Schultes. 

May we return again to the phenomena of micropsia and macropsia. It has 
been said — this is mostly Mr. Gordon Wasson, who is of the opinion that 
these drugs have played a very great role in religion (not only the Christian 
religion but previous religions as well) — that such things as the ideas of 
giants and dwarfs may have come from these intoxications. 

Can I ask Dr. Del Pozo, who is very familiar with the Mexican literature on 
this subject, if there are any indications of these distortions of perception in 
the Mexican literature. In other words, do the Gods have any definite size? 

Dr. Del Pozo : The Chroniclers describe the different hallucinatory visions 
that the Aztec priests used to have. They ate the mushrooms because they 
thought that those visions would provide them with some information about 
the future, or about the interpretation of different facts, but I don't know 
of any jDaritcular descriptions of macropsia. They usually mention devils, 
figures and colors. 

I had an experience, I would say a collective experience : We were working 
with mushrooms, and a group of young collaborators who joined to celebrate 
the birthday of one of them suddenly decided to go to the laboratory in the 
evening and eat mushrooms. 



378 



They were so worried a'bout the effects that they called me at about three 
o'clock in the morning. All of them were very amused because of the color 
visions, the forms and things that appeared to them. They were talking one 
to another and saying : "Look at this yellow color, look at this green color". 
I am sure they were simultaneous, but more or less the same type of visions. 
This makes me believe that it is a physiological action, in which there is 
little influence of the psychological background. There were no reports of 
macropsia or any other deformation in size. 

Dr. Szara : I would like to emphasize something here which has not been 
overlooked, but it has not been emphasized enough, and that is the tremen- 
dous importance of the set and the setting in determining the kind of reac- 
tion which a person can get. If you suggest to the subject that you are a 
little mouse or you are an amoeba, you feel like it, or if you. suggest that he is 
God, he is powerful, then he will have macropsia — so that setting is very, 
very important. I think here what Mr. Seitz has referred to, this initiation 
ceremony during the taking of the snuffs — the father tells the son what to 
expect, what to hallucinate and what to experience — is apparently very 
much imbedded into the ritual use of these drugs. 

Dr. Schultes: You asked me to define "hallucinogenic", and I forgot 
to do so. I believe that the man who coined this very useful and definitive 
word is Mr. Wassen. I am happy to note that in this meeting the etymologi- 
cally impossible word "psychedelic" has not frequently been used. 

One of the "psychedelic giants" asked my advice when he planned to use 
the term psychedelic in the title of a journal. I pointed out that one does 
not, in coining an English word from Greek roots, make a combination with 
"e" ; it is made with "o". The word then would have to 'be "psychodelic". He 
pointed out that psycho had acquired a very special meaning in English, and 
that it could not be used without intimating that specialized meaning. Still, 
with the many good terms available, this etymological error would seem 
superfluous. 

Chairman Dr. Holmstedt: May I at this point ask Dr. Daly or Dr. 
Homing what one would expect from a chemical point of view, when the 
OH group in tryptamines sits in the 4, 5, 6 and 7 position ? Would there be 
chemically important differences in these compounds? 

Dr. Horning : We made an observation some years ago, which was never 
published, for the hydroxy compounds. I think it is very clear that the 
properties would be different both chemically and, I am sure, physiologically, 
with different positions of subtitution. 

In the crystalline form, bufotenine has an ionic structure. However, by 
certain chromatographic techniques, it is possible to get a second form of 
bufotenine. I think that probably the second form has a phenolic amine 
(non-ionized) structure (Fig. 1) because of infrared spectroscopic evi- 
dence. It was obtained in the absence of polar solvents (a non-polar system 
was used) . 

I think it is fairly clear that in the ionized form, in a polar medium, the 
compound would not penetrate the blood-brain-barrier. This is one of the 
problems in talking about the 6-hydroxy compound, as Dr. Holmstedt said. 



379 




NON-IONIZED IONIZED 

FlQ. 1. 

Chairman Dr. Holmstedt : Why would it necessarily be in the 6-position ? 

Dr. Horning: This recalls the argument over specific and. non-specific 
hydroxylation. I think that the other isomers are formed, too, but they are 
hard to find. 

At any rate, the 6-position hydroxylation is a well-defined reaction. This 
would be the expected compound. On the other hand, I would expect no action 
for this metabolite. 

Dr. Szara : How about psilocybin? 

Dr. Horning : The question of active transport and mechanism of pene- 
tration into a cell runs through many areas of chemistry and pharmacology. 
If one has a phosphate, there may be an active transport mechanism. Also, 
polar compounds including glucose enter the brain. "Active transport" exists, 
although we know very little about the mechanism. 

Dr. Szara : Psilocin is a free hydroxy. It has no phosphate. 

Dr. Horning : I would ask what your own view of this is, since you have 
studied it so extensively. 

Dr. Szara : What my feeling is about the hydroxy derivatives is that they 
don't have to penetrate the brain all the way, entirely. It might be enough 
to penetrate only some trigger points, where the blood-brain-barrier is more 
leaky, like the hypothalamus or other areas which have been shown to be 
able to let larger molecules through. It might be enough for a hydroxy 
derivative to penetrate those areas and produce some very fine regional 
changes, and this is, I think, really what happens with the hydroxylated 
derivatives. 

Dr. Horning : You may not need to postulate transport as such. 

Dr. Szara: This is hypothesis, really. I might mention here that the 
6-flurodiethyltryptamine is equally lipid soluble, and it penetrates the brain 
but is not hallucinogenic. 

Dr. Horning : You feel that the 6-position is indeed critical ? 

Dr. Szara : It might be. 

Dr. Horning : I have one other thing to say : Dr. Holmstedt has been a 
pionere in many ways, and one of the ways is in the chemical techniques he 
is using to deal with these compounds. It is possible to study all of the ma- 
terials in small quantities by gas chromotography, and this is due largely 
to a whole series of developments, not the least of which was the development 
in Stockholm by R. Ryhage of the "molecule separator". This permits the 
use of gas chromatography and mass spectrometry in a combined fashion. 



380 



This is at present the most powerful chemical way we have of investigating 
substances. I think this work will point the way for both pharmacologists and 
chemists, and investigations may go faster in the future. 

I will ask if Dr. Daly agrees with any of these comments? 

Dr. Daly: It may be that in 4-hydroxytryptamines such as psilocybin, 
the nitrogen and the phenolic hydroxy group may interact intramolecularly 
in such a way as to increase the lipid solubility over that of other hydroxy- 
trytamines, and thus facilitate penetration into the brain. Again, while 
we assume that hydroxylation of tryptamines occurs only in the liver, we 
have no good proof that such hydroxylations do not take place in certain 
specific areas of the brain, in which case the hydroxytryptamine would be 
formed in situ, and would not have to penetrate the blood-brain-barrier. 

In keeping with this idea, we thought to develop a sensitive assay for 6- 
hydroxylation based on the release of tritiated water from 6-tritiotryptamine 
on enzymatic hydroxylation. On studying this transformation with liver 
microsomes, we found that the tritium atom migrated to another position in 
the aromatic ring as a result of 6 -hydroxylation. Similar migrations occur 
during the hydroxylation of other aromatic compounds, and cognizance of 
this unusual reaction should allow us to develop a sensitive and specific 
assay for the hydroxylation of tryptamines. 

Regarding recent reports on hydroxylation of indoles in other than the 
6-position, one finds that microsomal enzymes usually hydroxylate in posi- 
tions of high electron density, so that for a 5 -methoxy indole in which the 
electron density is higher in the 4- rather than the 6-position, one might 
expect preferential hydroxylation of the 4-position. We have done studies on 
microsomal hydroxylation of melatonin (S-methoxy-iV-acetyltryptamine), 
and have isolated three products. The major product is 6-hydroxy melatonin, 
while one of the others has properties compatible with those expected of 
4-hydroxymelatonin. 

Our microsomal studies on hydroxylation of tryptamines support Dr. 
Szara's statement that the 6-fluorotryptamines do not undergo hydroxylation. 
Since 5-fluorotryptamines do undergo hydroxylation, to form what we be- 
lieve is 5-fluoro-6-hydroxytryptamines, in vivo evaluation of the hallucino- 
genic properties of 5-fluoro-N,N-dimethyltryptamine would be of interest. 

The 5-m6thoxy-N,N-dimethyltryptamine, found in plants and an active 
component of certain South American snuffs, also occurs in the skin of a 
certain toad. The presence of large amounts of this compound in these toads, 
and the occurrence in other toads of structurally related tricyclic indoles 
(dehydrobufotenine), led Dr. Witkop and myself to our present studies on 
0-methylnordehydrobufotenine, the cyclic analog of the 5-methoxy-N,N- 
dimethyltryptamine. This tricyclic indole prepared under the auspices of the 
Psychopharmacology Research Branch, NIMH, has CNS activity which is, 
however, markedly different from the open chain analog. 

I would like to ask Dr. Holmstedt whether during his studies on the gas 
chromatographic and mass spectral analysis of snuffs, he also investigated 
the 4-methoxy, 6-methoxy and 7-methoxy-7V^,A^-dimethyltryptamines, which 
would have virtually the same mass spectra as the 5-methoxy compound ? 



381 



Chairman Dr. Holmsteot : That is right, but we have previously shown 
that the methoxy group was in the 5-position by using spectrofluorometric 
techniques and changing the pH of the sokition ; furthermore GLC resolves 
position isomers. This proves once more liow advantageous the combination 
gas chromatrography-mass spectometry is. 

Dr. Daly : This might be worth looking at, whether other methoxy com- 
pounds occur which may not be separated in the snuffs and have hallucino- 
genic activity. 

CHAnoiAX Dr. Holmstedt : Wliy has not anyone studied the 4:-methoxy- 
NjN-dimethyltryptamine ? 

This session started out with anthropology, covered botany and pharma- 
cology, and it now ends on a chemical note. I think it has been a good 
combination. 

Thank you all. 



382 



SESSION V 



AYAHUASCA, CAAPI, YAG£ 

Daniel H. Efron, Chairman 



Psychotropic Properties of the 
Harmala Alkaloids 

Claudio Naranjo 

Department of Anthropological Medicine 
University of Chile, Santiago, Chile 

The use of plant materials containing harmala alkaloids is probably very 
old. Peganum harmala, a zygophyllaceous plant, the seeds of which contain 
harmine (i), harmaline (2), and harmalol (3), is thought to be native to 
Russian Turkestan or Syria, and has been used throughout the Middle East 
both as a spice and as an intoxicant. Its medical and psychotropic properties 
are known in India, where it was probably taken by the Moslems, and where 
the seeds may now be purchased in bazaars (^) . It is also believed that it was 
the Arabs who took the plant along the African Mediterranean and into 
Spain, where it may be found growing wild at present. 

The species of Bamdsteriopsis that constitute a source of harmala alkaloids 
are used in an area lying between the rain forests of South America and the 
Andes. This is approximately the area designated as the "montana" in the 
classification of South American cultures. It consists of a tropical elevated 
territory along the headwaters of the Amazon and Orinoco Rivers, where 
live some of the least known Indian groups. 

Of much interest is the recent discovery of substances closely related to 
the harmala alkaloids in animals. One of these is adrenoglomerulotropine, a 
hormone of the pineal body, the chemical identity of which has been indi- 
cated as 2, 3, 4, 9-tetrahydro-6-methoxy-l-methyl-lH-pyrido(3, 4, 6) indole 
(6). This substance is identical to 6-methoxytetrahydroharman which has 
been shown to be formed in vivo from 5-methoxytryptamine and acetalde- 
hyde (6). 6-Methoxytetrahydroharman is an isomer of tetrahydroharmine, 
one of the alkaloids in Banisteriopsis (7), and in the African Leptactinia 
densifjora (8). One more substance, 6-methoxyharmalan, has been shown 
to derive, at least in vitro, from melatonin (9), which in turn results from 
the methylation of acetyl serotonin. The enzyme which makes this methvla- 
tion possible, hydroxyindole-O-methyltransf erase (HIOMT), has only been 
found in the pineal body. (See Fig. 1.) 

6-Methoxyharmalan is an isomer of harmaline differing in the position of 
the methoxy group, which is attached to the same point of the ring as the 
phenolic group in serotonin or the methoxy group in ibogaine, a demon- 
strated hallucinogen (10). (See Fig. 2.) 

As will be seen in the rest of the paper, I have found both synthetic 6- 
methoxyharmalan and 6-methoxytetrahydroharman to be hallucinogenic 
(11), a fact which invites speculation on the possible role of the metabolites 
on the psychoses. It is suggestive that the highest concentrations of serotonin 
have been found in the pineal glands of schizophrenics, and that 6-methoxy- 
harmalan is a powerful serotonin antagonist. 



385 




5-methoxytryptamine 6-methoxytetrahydroharman 

Fig. 1. 




CH3 CH3 

6-methoxyharmalan 6-methoxytetrahydroharman 




ibogaine tetrahydroharman 



386 



Fig. 2. 



It may be noted that the above reported finding constitutes the first demon- 
stration of an endogenous hallucinogen, twenty years after the motion of a 
psychotoxic metabolite was proposed by Hoffer, Osmond and SmythieS (12). 

Lastly, one may wonder whether the pineal body — associated by Tibetan 
traditions with higher states of consciousness — may not actually play a part 
in the regulation of attention or the rhythm of sleep and wakefulness. An 
indirect indicated of this is the demonstration of increased pineal HIOMT 
activity in rats kept in constant darkness for six days (13). 

Studies carried out some 30 years ago by Gunn et al., showed that some 
synthetic &ete-carbolines had similar pharmacological properties, which in 
turn resembled those of quinine (14.). Thus, both quinine and the harman 
derivatives were toxic to protozoa, inhibited the contraction of the excised 
muscle of the frog, caused relaxation of most smooth muscle, but contraction 
of uterine muscle, and caused convulsions followed by paralysis in mammals. 

The only compound in this chemical group reported to have hallucino- 
genic properties, to my knowledge, is harmine (15) , which may be regarded 
as identical ^o telepathine, yageine, and banisterine, and constitutes most of 
the alkaloid content in the Bardsteriopsis extracts. Yet the question poses 
itself as to whether the qualitative similarity of harman derivatives, as evi- 
denced by many pharmacological effects, would also apply to the psycholog- 
ical syndrome produced. For instance, Gunn finds that harmaline is twice 
as active as harmine, judging from the lethal doses of both compounds for 
the rabbit, and from their toxicity to protozoa. I have indeed found har- 
maline to be hallucinogenic at dosage levels above 1 mg./kg. i.v. or 4 mg./kg. 
by mouth, which is about one half the threshold level for harmine. It may 
be interesting to note at this point that the onset of effects of harmaline or 
other derivatives is about one hour after ingestion by mouth, but almost 
instsmtaneous after intravenous injection, if circulation time from elbow to 
brain is taken into account. In this, harmaline resembles the chemically re- 
lated tryptamines and differs from the slow-acting phenylethylamines. 

Tetrahydroharmine, the reduction product of harmaline, is another sub- 
stance studied by Gunn and shown to be similar to its more saturated homo- 
logs, but three times less active than harmaline. 

Kacemic tetrahydroharmine, up to the amount of 300 mg. by mouth, was 
administered by us to one volunteer, who reported that at this dosage level 
there were subjective effects similar to those he experienced with 100 mg. 
of -harmaline. More trials would be required to assess the mean effective dosage 
of tetrahydroharmine as a hallucinogen, but this single experiment suggests 
that racemic tetrahydroharmine is about one-third as active as harmaline, 
corresponding to Gunn's estimation on the basis of lethal dosage. 

The effect of relocating the methoxy group of harmaline was not tested by 
Gunn but was of special interest here, in view of a possible function of the 
6-methoxy homolog in the body. 6-Methoxyharmalan was indeed shown 
to be hallucinogenic, as was anticipated, subjective effects becoming apparent 
with approximate oral dosages of 1.5 mg./kg. The ratio between threshold 
doses of harmaline and its 6-methoxy analog is 3 :2, 6-methoxyharmalan 
being the more active. 



387 



6-Metlioxytetrahydroharman, probably identical with pineal adreno- 
glomerulotropine, was also shown to be psychoactive, eliciting mild effects 
at a dosage level of 1.5 mg./kg. The relative activities of the two 6-m.eth- 
oxyharmans are approximately 1 :3, the harmalan being more active than its 
unsaturated homolog, which confirms once more Gunn's statement as to the 
relationship between double bonds and pharmacological effect. 

It would seem premature to make any statement as to whether there is a 
qualitative difference in the subjective reaction to the different carbolines 
tested. Such appeared to be the case, in that experiences with the 6-methoxy 
compounds happened to be of a less hallucinogenic nature in the strict 
sense of the word, their effect being more akin to a state of inspiration and 
heightened introspection. Among the 7-methoxy compounds, harmaline 
seemed to cause more withdrawal and lethargy than harmine, but both sub- 
stances showed a highly hallucinogenic quality in the visual domain. How- 
ever, more systematic study would be needed to confirm differences such as 
these, in view of the variability which exists even between consecutive ex- 
periences of the same individual with the same chemical. This is well known 
for LSD-25, and was quite marked in four of the seven subjects to whom 
harmaline was administered more than once. Yet it seems clear that the 
various &ete-carbolines are similar enough in their effect to be told apart 
from mescaline, as was shown by the comments of persons to whom mescaline, 
harmaline and some other barman derivative were administered on con- 
secutive occasions. The third compound, the nature of which was not known 
to the experimental subjects, was invariably likened to harmaline rather than 
to mescaline. The same can be said of instances in which harmaline was admin- 
istered on a second or third occasion without divulging the drug's identity. 
Regardless of the differences between consecutive harmaline experiences, 
these were classified together as distinct from that of mescaline. 

It is quite possible that further research with a larger number of subjects 
may demonstrate qualitative differences of a subtle kind between the differ- 
ent carbolines, analogous to those shown for variously substituted phenyl- 
isopropylamines {16^ 17). Nevertheless, it may be adequate for the time 
being to regard the effects of harmaline as an approximately valid indica- 
tion of a syndrome shared, with minor variations, by compounds of similar 
structure. 

This information that I am presenting here on the effects of harmaline is 
based on the reactions of 30 volunteers to whom the drug was administered 
as a hydrochloride, either by mouth or intravenously, under standard con- 
ditions. One aspect of these was the absence of all information regarding 
effects other than those primarily psychological in nature. 

As part of the interest lay in knowing the difference between the harmaline 
syndrome and that of mescaline, both drugs were administered to each 
volunteer on different occasions. 

In the case of every one of the 30 subjects it was evident to the observer 
that both the subjective and behavioral reactions of the person were quite 
different for the two drugs, and this was corroborated without exception by 
the subjects themselves. Yet the quality of the difference was not clearly 



388 



the same in all instances, so that it is hard to find re^larities to which no 
exception can be mentioned. Recurring differences between harmaline and 
mescaline can be observed however, and in what follows, the most salient of 
these are cited. 

Physical sensations in general are more a part of the harmaline intoxication 
than of that produced by mescaline (or similar substances). Parasthesias 
of the hands, feet or face are almost always present with the onset of effects, 
and are usually followed by a sensation of numbness. These symptoms are 
most marked when the alkaloid is injected intravenously, in which case some 
subjects have likened them to those experienced under ether anesthesia. Dis- 
tortions of the body image, which are quite frequent with mescaline or 
LSD-25, were very exceptional with harmaline. Instead, subjects indicated 
isolated physical symptoms such as pressure in the head, discomfort in the 
chest, or enhancement of certain sensations, as those of breathing or blinking. 

Nausea was reported by 18 subjects and this sometimes led to intense 
vomiting. It was usually associated with dizziness or general malaise, which 
would in turn appear or disappear throughout a session in connection with 
certain thoughts or stimuli. 

In the domain of perception, one of the most noticeable differences between 
the drugs is in the visual appearance of the environment. While distortions 
of forms, alterations in the sense of depth and changes in the expression of 
faces are of frequent occurrence under most hallucinogens, these phenomena 
were practically never seen with harmaline. The same was true in regard 
to color enhancement, or perception of apparent movement — flowers breath- 
ing, shapes dancing and so on — frequently seen with LSI)-26. With harma- 
line, the environment is essentially unchanged, both in regard to its formal 
and its aesthetic qualities. Phenomena which most frequently occur with 
open eyes are the superposition of images on surfaces such as walls or ceilings, 
or the viewing of imaginary scenes simultaneously with an undistorted per- 
ception of surrounding objects. Such imagery is not usually taken for 
reality but there was an exception to this in the case of a man who saw a 
cat climbing a wall, then turning into a leopard, when in fact, not even 
the cat existed. 

Other recurrent visual phenomena were a rapid lateral vibration in the 
field of vision and double or multiple contours in objects, especially when 
these were in motion or when the subject's eyes turned away from them. 
Some described lightning-like flashes. 

With closed eyes, imagery was abundant and most often vivid and bright 
colored, with a predominance of red-green or blue-orange contrasts. Long 
dream-like sequences were much more frequent for harmaline than for 
mescaline. Certain themes, such as felines, negroes, eyes, and flying are fre- 
quent and have been reported elsewhere {18) . 

Perception of music was not altered or enhanced with harmaline as is the 
case with mescaline or LSI)-25. Yet noises became very prominent and gen- 
erally bothersome. Buzzing sounds in the head were reported by more than 
half of the subjects. 

Synaesthesias were not reported, and the sense of time was unaltered. 



389 



Many of the differences between harmaline and mescaline may be related 
to the facts that the effect of the former on the emotions is much less than 
that of mescaline, and thinking is affected only in subtle ways, if at all. 
Concern with religious or philosophical problems is frequent, but there is 
not the aesthetic or emphathetic quality of the mescaline experience. Thus, 
the typical reaction to harmaline is a closed-eye contemplation of vivid 
imagery without much further effect than wonder and interest in its sig- 
nificance, which is in contrast to the ecstatic heavens or dreadful hells of 
other hallucinogens. Despite this lesser effect of harmaline on the intensity 
of feelings, qualitative changes do occur in the emotions, which may account 
for the pronounced amelioration of neurotic syptoms evidenced by 8 of our 
30 subjects, as detailed in a separate report {19) . 

Desire to communicate is slight under the effect of harmaline, since other 
persons are felt to be a part of the external world, contact with which is 
usually avoided. Possibly related to this withdrawal is the extreme passivity 
which most subjects experienced in regard to physical movement. Most of 
them lay down for 4 to 8 hours and reported a state of relaxation in which 
they did not feel inclined to move a muscle, even to talk. In view of this 
observation, it is hard to understand how the Indians, according to some 
authors (W) , engage in dancing or even whip one another under the effects of 
caapi. 

Summing up, harmaline may be said to be more of a pure hallucinogen than 
other substances whose characteristic phenomena are an enhancement of 
feelings, aesthetic experiences, or psychotomimetic qualities such as paranoid 
delusions, depersonalization, or cognitive disturbances. Moreover, harmaline 
appears to be more hallucinogenic than mecaline (the most visually acting 
drug in its chemical group) , both in terms of the number of images reported 
and their realistic quality. In fact some subjects felt that certain scenes which 
they saw has really happened, and that they had been as disembodied wit- 
nesses of them in a different time and place. This matches the experience of 
South American shamans who drink ayahuasca for purposes of divination. 

The remarkable vividness of imagery viewed under the effect of harmaline, 
together with phenomena such as double contours and persistence of after 
images, had led us to suspect a peripheral, i.e. retinal, effect of the drug, 
and this was tested by the recording of electroretinograms in cats. The 
suspicion was confirmed, in that harmaline causes a definite increase in the 
alpha wave and a decrease in the beta wave of the electroretinogram, both 
of which become apparent before any change is observed in the brain cortex. 

It would be beyond the scope of this paper to deal with electrophysiological 
studies, but I will briefly mention some recent results we have obtained in 
cat experiments at the University of Chile, which add to the general picture 
of the harmaline intoxication : 

(1) Electrocorticograms recorded in chronically implanted cats showed 
either electrocortical desynchronization or synchronization in correspondence 
with the animal's behaviour, alternating between arousal and lethargy. In 
addition to this spindle bursts of high voltage and low frequency were 
observed in all instances and these did not seem to be related to the animal's 
behaviour. 



390 



(2) Experiments performed in cats with a chronically isolated forebrain 
showed even more clearly the above mentioned spindle bursts in the brain 
cortex, and regular wave bursts of high voltage in the pontine reticular 
formation, which we have not seen described under other pharmacological 
conditions. These cats were behaviourally overactive. 

These facts may be interpreted as an indication that harmaline acts 
as a stimulant on the midbrain reticular formation. The direct action of 
harmaline on the brain cortex is hard to interpret and seems more that of a 
depressant, but this is counteracted in the intact animal by the arousing 
influence of the reticular formation. The neurophysiological picture matches 
well that of traditional yage "dreaming", in that the state we have described 
involved lethargy, immobility, closed eyes and generalized withdrawal from 
the environment, but at the same time an alertness to mental processes, and 
an activation of fantasy. 

REFERENCES 

( jf ) GoEBEL, Annalen, 38, 363, 1841. 

(2) Feitsche, Annalen, 64, 365, 1847. 

(3) FiscHEK, O., Chem. Soc. Abstr., 1901 (i) , 405. 

(4) Maxwell, M. M. "Caapi, its source, use and possibilities." Unpubl. MS., 1937. 

(5) Fakeel, G. and W. M. McIsaac, "Adrenoglomerulotropin." Arch. Biochem. Biophys., 

94 : 443-544, 1961. 

(6) McISAAC, W. M. "Formation of l-metliyl-6-methoxy-l,2,3-tetraliydro-2-carboline 

under physiological conditions." Biochem. Biophys. Acta 52 : 607-609, 1961. 

(7) HocHSTEiN, F. A. and A. M. Paradies. "Alkaloids of Banisteria Caapi and Pres- 

tonia Amazonicum." J. Am. Chem. Soc. 79, 5735, 1957 

(8) Paris, R. R., F. Percheron, J. Manlil and Goutarel. Bull. Soc. Chim. France, 

750, 1957. 

(9) McIsAAC, W. M., P. A. Khaieallah and I. H. Page. "10-methoxyharmalan, a potent 

serotonin antagoinist which affects conditioned behaviour." Science 134, 674-675, 
1961. 

(10) Naranjo, C. Psychological effects of Ibogaine. In preparation. 

{11) Naranjo, C. and A. Shtjlgin. Hallucinoerenic properties of a pineal metabolite: 

6-methoxytetrahydroharman. Science. In press. 
(,12) HoFFEE, A., H. Osmond and J. Smythies. "Schizophrenia : a new approach II." J. 

Ment. Sci., 100 : 29-45, 1950. 
(IS) AxELROD, J., R. J. WuRTMAN, and S. Snyder. "Control of hydroxyindole-O-methyl- 

transferase activity in the rat pineal gland by environmental lighting." J. Biol. 

Chem. 240 : 949-954, 1965. 

(14) GuNN, Arc. Int. Pharmacodyn., 50, 793, 1935. 

(15) Pennes, H. H., and P. H. HocH, Am. J. Psychiat. 113, 885, 1957. 

(16) Shulgin, a., T. Saegent and C. Naranjo. "Chemistry and psychopharmacology of 

nutmeg and related phenylisopropylamines." Paper presented at the Symposium 
"Ethnopharmacologic Search for Psychoactive Drugs." U. of Calif., S. F., 1967. 

(17) Naranjo, C. MMDA in the facilitation of psychotherapy. Book in preparation. 

(18) Naranjo, C. "Psychological aspects of the yage experience in an experimental 

setting." Paper presented at the Annual Meeting of the American Anthropological 
Association, 1965. 

(19) Naranjo, C, Ayahuasca, the Vine of the Dead. Book in preparation. 

(20) Taylor, N., Flight from Reality. 1949. 

(21) ViLLiBLANCA, J., C. Naeanjo, and F. Riob6. Effects of harmaline in the intact cat 

and in chronic isolated forebrain and isolated hemisphere preparations. Psycho- 
pharmacologia. In press. 



391 



The Making of the Hallucinogenic 
Drink from Banisteriopsis 
Cuapi in Northern Peru 

Dermot Taylor 

Department of Pharmacology, University of California 
Los Angeles, California 

A moving-picture film showing the ceremonies and procedures for 
preparation of the drink was presented. 



392 



Chemical Compounds Isolated from 
Banisteriopsis and Related Species 

Venancio Deulofeu 

Facultad de Ciencias Exactas y Naturcdes, Buenos Aires, Argentina 

The Malpighiaceae, to which the genus Banisteriopsis belongs, is a family 
distributed in tropical and sub-tropical humid regions of Africa and Amer- 
ica. The genus Banisteriopsis is represented by about 75 species, which grow 
in America from Mexico and Cuba to Argentina, most of them in South 
America {!)• 

Only a few species of Banisteriopsis have been investigated chemically, 
and the first stimulus for the chemical work was the finding in the middle 
of the last century by the British explorer Spruce that a woody vine, which 
he classified as Banisteria caapi, later known as Banisteriopsis caapi^ was the 
main ingredient employed in the preparation of an intoxicating drink by 
certain tribes living in the Amazonian Brazil. It was later found that the 
preparation and use of a similar beverage extended to a larger region, to 
what is today known as the eastern parts of Colombia, Ecuador, Peru and 
Bolivia, where it was given different vernacular names: ayahuasca, caapi, 
yage, yaje, natem, natema, etc., names which were also applied to the plants 
employed for their preparation. Other plants were added and mixed with 
the former. 

The history of the botanical, chemical and pharmacological implications 
of the beverage has been told in several opportunities and from several angles 
3) . While at the beginning there were difficulties in the identification of 
the alkaloids isolated from the extracts of the plants, and which were made 
responsible for the activity of the intoxicating drink, it seems that today, 
with the improvement of the methods of identification and the use of new 
techniques, we know exactly which are the bases isolated. There seem to be 
more difficulties from the botanical side. Th6 lack in many chemical studies 
of plant specimens, or of a rigorous identification of the botanical material 
worked by the chemists, makes it impossible to know exactly which were 
the species employed. It is with this qualification that some of the botanical 
names are quoted in this paper. 

Early chemical investigation of the plant employed in Colombia by the 
natives indicated the presence of an alkaloid which was given the name of 
telepathine as early as 1905 by Zerda Barron (^). A base supposed to be 
responsible for the activity of the drink was isolated in 1923, no doubt in im- 
pure form, by Fischer Cardenas (5) who conserved the name of telepathine. 

Another isolation was carried out two years later by Barriga Villalba ((5), 
who seems to be the first who obtained a crystalline product, to which he 
gave the name of yajeine. From the assigned formula, CiiHgNsOg and from 
its m.p.206°, we have now to conclude that it was an impure substance, al- 



262-016 0-67— 27 



393 



though the lack of rotation is in agreement with what can be expected for 
an aromatic /3-carboline structure. Another base was present in the mother 
liquors and named yajenine, but no constants were mentioned in the paper. 
According to Barriga Villalba, he worked the stems of a vine which was 
known by the vernacular name of yaje, and which according to Reinburg was 
Haemadictyon amasonicum (Prestonia amasonica Spruce), which is an Apo- 
cynaceae. Rios, in his review on the ayahuasca, mentions that in a later paper, 
Barriga Villalba states (7) that the plant he worked was not P. amazonica, 
but B. caapi, which is in agreement with the investigations of Schultes and 
Raffauf {8) on the use of the former species as a narcotic. 

From what can be considered an authentic specimen of B. caapi, Perrot 
and Raymond-Hamet {2) isolated for the first time in pure condition one of 
the bases present in the plant (m.p.258°), for which they conserved the name 
of telepathine. A year later Lewiri {9) described the isolation of an alkaloid 
from the same source, which he called banisterine. In his paper, Lewin says 
that the chemists from E. Merck (Darmstadt, Germany), considered banis- 
terine identical to the base harmine (/), an alkaloid isolated more than a 
century ago from Peganwm harmala L. (Zygophyllaceae). Two papers on 
the identification were published the same year almost simultaneously ; one 
by Elger {10) and the other by Wolf and Rumpf {11) , the latter workers being 
members of the Merck laboratories. 

Elger employed plant material supplied by Raymond-Hamet and which 
was identified as B. caapi, according to A. W. Hill, then Director of the Kew 
Botanical Gardens. Sir Robert Robinson compared the alkaloid isolated by 
Elger (m.p.263-264°), with the harmine (/) from P. harmala, and with a 
synthetic sample, and concluded that they were identical. He comments on 
the difficulties of purifying harmine, which can explain the low melting point 
of the base obtained by Barriga Vallaiba. Chen and Chen {12), who worked 
also with an authentic botanical specimen, confirmed the identification, and 
could isolate harmine from stems, leaves and roots. 

A plant identified as B. caapi Spruce was investigated many years later 
by Hochstein and Paradies {13). It was harvested near Iquitos, in Peru, 
where it was named ayahuasca. They confirmed the presence of harmine (I) 
and isolated also harmaline (II) and ( -h ) -tetrahydroharmine (III). They 
state that the two latter alkaloids were found in a rather large amovmt. 
The same bases were also present in an aqueous extract of the plant "as 
used by the natives" but which appeared richer in harmaline and tetrahydro- 
harmine than the extracts of the plant. They suggested that these two alka- 
loids may be the most active psychotomimetic components of the extracts. 

All the bases isolated from B. caapi have a y8-carboline skeleton, with 
diflferent degrees of hydrogenation in the pyridine ring. Their structure was 
already known because of the interest of the chemists in similar alkaloids 
isolated from P. harmala Z., harmine (I) and harmaline (II), which culmi- 
nated in the synthesis of harmaline (II) by Manske, Perkin and Robin- 
son {lit). 

Although the racemic tetrahydroharmine had already been prepared in 
the laboratory, it was the first time that one of the enantiomers, ( -|- ) -tetra- 



394 





hydroharmine (III), had been found in Nature. The dextro compound iso- 
lated by Hochstein and Paradies (13) was in fact a new natural base, and 
because of its pharmacological activity it was of interest to determine its 
absolute configuration. This was done recently by Koblicova and Trojanek 
who found that its asymmetric carbon atom has the same chirality as 
the asymmetric carbon of D-alanine (IV), which is opposite to that of the 
protein aminoacid L-alanine. 

Another species investigated has been B. inebrians Morton. O'Connell and 
Lynn {16) isolated harmine (I) from the stems of an authentic specimen 
collected by Schultes, and found that the leaves probably contains the same 
base. They could not detect harmaline nor harmalol. The same species was 
worked again by Poisson {17) in 1965, the plant being collected in a place 
named Nazareth, on the shores of the Maranon River, in Peru. He confirmed 
the presence of harmine in the stems and pointed out that another base, with 
the chromatographic properties of harmaline (II), was present in small 
amount. 

Poisson investigated also the leaves of another species, B. rusbyana 
(Niedenzu) Morton, known to the natives as yaje, which were added to the 
stems of B. inebrians when ayahuasca was prepared. Surprisingly, this 
species did not contain alkaloids with a ^-carboline structure, and the only 
base which he could identify was dimethyl-tryptamine ( V) . The amount was 
rather high (0.64%). 

The species worked by Poisson were identified by Cuatrecasas. The finding 
of dimethyltryptamine (V) in B. rusbyana^ a species used together with 
B. inebrians for the preparation of ayahuasca, is interesting for several 
reasons. One is that the same base was isolated by Hochstein and Paradies 
{13) from the extract of a plant which they considered to be P. amazonica, 
which received the local name of yage, and which was used by the natives 



395 




(¥) 

to prepare ayahuasca as an additional component to B. caa'pi. Hochstein 
and Paradies received only an extract of the plant, whose identification is 
doubtful (5, 18). 

The second point of interest is that bases of the tryptamine type are 
typical components of other plants which have been used by the natives in 
many places of South America and in the Caribbean, for the preparation 
of intoxicating snuffs. They belong to the Piptadenia (Leguminosae) {19) 
and Virola (Myristicaceae) genus {20). 

Other BanisteHopsis species have been mentioned as the main or addi- 
tional ingredients employed in the preparation of ayahuasca. They are 
B. quitensis (Ndz) Morton {21), which according to Cuatrecasas {le) is 
identical to B. caapi Spruce, B. longialata {21), and B. metaUicolor Juss. 
{B.lutea Ruiz) {3). 

I have not found in the literature any indication that authentic specimens 
of those plants have been submitted to chemical research, but because they 
are used in the preparation of intoxicating drinks, their investigation will 
be of much interest. 

On the other hand, B. crysophylla Lam. a species which grows in Aus- 
tralia, is reported to contain alkaloids {22) and B. nitrosiodora Griseb, 
which is one of the species found in Argentina, is practically devoid of 
alkaloids {23). There remain a large number of species which have not even 
been submitted to a preliminary chemical investigation. 

Harmine (I) has been isolated by Mors and Zaltzman {2 If) from the stems 
and leaves of another South American Malpighiaceae, Oabi paraensis Ducke, 
which is closely related to the Banisteriopsis genus. It grows in Brazil, in 
the upper Amazonian region and also in Peru {3). According to Duke {26), 
it is employed in popular medicine, although not for the preparation of 
intoxicating drinks. 

It is worthwhile to note that only a few other species of Malpighiaceae 
have been investigated for alkaloids. One of them is Lophantaera lactecens 
{L. longifolia) which grows in the Amazonian, and is employed for the 
preparation of a kind of tea. Kibeiro and Macliado {26) isolated from ex- 
tracts of that plant a new base, lophanterine, which structure is unknown. 

In his review on the Botanical Sources of the New World narcotics, 
Schultes {21) mentions in i-elation with the preparation of ayahuasca, two 
Malpighiaceae which, if botanical material became available, will deserve 
chemical attention. They are Tetrapterys methystica, from which an halluci- 



396 



nogenic drink is prepared in Colombia, on the limits of Brazil, and Mas- 
cagnia psilophylla var. antifebrilis, which was pointed out by Niedenzu as 
a source for the preparation of ayahuasca which in the opinion of Schultes 
is doubtful. 

To my knowledge harmine (I), harmaline (II) and tetrahydroharmine 
(III), have never been isolated from other original American plants. They 
have been found to be present in intoxicating snuffs prepared by the natives 
from unknown botanical sources. We have two almost simultaneous reports. 
One is by Biocca, Galeffi, Montalvo and Marini-Bettolo (^7), who from a 
snuff prepared by Tukano and Tariana Indians living in the valley of the 
Uaupes River, isolated harmine (I), harmaline (II) and tetrahydroharmine 
(III), exactly the same bases found in B. caapi by Hochstein and Paradies 
(13). According to the Italian authors, the snuff is named parica and is 
prepared from a vine, which is also employed for the preparation of a drink. 
The species remained imdetermined. 

On the other hand, Bernhauer {2S), has investigated a snuff employed by 
the Surara and Pakidai Indians, living near the River Demeni, a subsidiary 
of the Negro River, which he says is known as parica, yopo, ebena or epena. 
He could isolate harmine (I) and ( + ) -tetrahydroharmine (III), while 
harmaline (II) was absent. The series of names given by Bernhauer to the 
drug that he investigated, shows how confused is its identification because 
samples of snuffs named epena, which were investigated not long ago by 
Hohnstedt (20) and Marini Bettolo, Delle Monache and Biocca (£9) , con- 
tained only tryptamine bases. In my opinion this is a nice proof of the im- 
portance of the future interdisciplinary work, which is needed to clarify 
the botanical sources and the chemically active substances in the plants and 
in the drugs prepared by the natives. 

Both types of bases isolated from Banisteriopsis species are related to 
tryptamine. Tryptamine or a precursor, is one of the intermediates in the 
biogenesis of a large number of indole alkaloids, most of them with a more 
elaborate structure than the simpler /3-carboline bases. 

The type and distribution of the simple tryptamine bases found in 
plants have been recently reviewed (30). Work done in several laboratories 
in recent years have shown that bases with a typical ^S-carboline structure are 
also, like the tryptamines, not restricted in botanical or geographical distri- 
bution (see Table I). 

The earlier representatives were isolated from Peganum harmala L. 
(Zygophyllaceae) more than a hundred years ago: harmaline (II) (1841), 
and harmalol (XVIII) (1841). The simplest base, harman (XI), was iso- 
lated from a Rubiaceae growing in Brazil in 1861 (Arariba rubra Mart., 
Sickinga rubra K. Schumm), and a few years later (1878) from Bymplocos 
racemosa (Symplocaceae) , indigenous to India. 

Research in the last few years has lead to the isolation of other /8-carbo- 
lines from plants growing in America. Bachli et al. (31), were isolated from 
Strychnos melinoniana Baill. (Loganiaceae), the quaternary base which is 
known as melinonine-F (XIV), and Antonaccio and Budzikiewicz {32) 



397 



Table I. Othee ^-Caeboline Bases Found in Plants" 




(SET) Csr) R = H ;CX2r) R = CH3 




Cm) (JM) Cm) R = H ; CXX) R = CH3 



(XI) Harman. Peganum harmala L. (Zygophyllaceae) ; Pasaiflora spp. (Passifloraceae) 
(39) ; P. incarnata L. HOj il) ; Calligonum minimum Lipski (Polygonaceae) (i2). 

(XII > 2V-Methyl-t€trahydiro-j3-carboline. Hammada leptoclada M. Iljln (Arthrophytum 
leptodadum Popov) (Chenopodiaceae) (43). 

(XIII) Harman-3-carboxylic acid. Aspidosperma polyneuron Mull. Arg. (Apocynaceae) 
(38). 

(XIV) Mellnonine F. Strychnos meJinoniana Baillon (Loganiaceae) (31). 

(XV) Tetrahydroharman, elaeagnine (R = H). Petalostylea lahicheoides R. Br. (Legu- 
minosae) (44) ; Elaeagnus angustif-oUa L. (Elaeagnaceae) (45) ; Leptactina densiflora Hook, 
f. (Rublaceae) (38) ; Hammada leptoclada M. Iljln (46) ; Calligonum minimum Lipski (42). 

(XVI) 2V-Methyl-tetrahydroharman, leptocladlne (R=CHa). S. leptoclada M. Iljln (43) ; 
Acacia complanata A. Cunn. (Leguminosae) (47). 

(XVII) Harmol. P. incarnata L. (40) ; Zygophyllum fdbago L. (Zygophyllaceae) (48). 

(XVIII) Harmalol. P. harmala L. 

(XIX) Tetrahydroharmol (R=H). Elaeagnus angustifolia L. (49). 

(XX) 2\r-Methyl-tetrahydroharmol (R = CH3). E, angustifolia L. (49). 

" This list of species is not exhaustive. They have been selected to show the distribution of 
bases in different families. 



harman-S-carboxilic acid (XIII) from Aspidosperma polyneuron Miill. Arg. 
(Apocynaceae) . 

Kecently, in our laboratory Sanchez and Comin {33), found /?-carbolines 
in Aeschrion crenata Veil., a Simaroubaceae which grows is Southern Brazil, 
Paraguay and Argentina. Although it is used in popular medicine, there is 
no indication that its extracts have intoxicating properties. The bases crena- 
tine (VI) and crenatidine (VII) were isolated, together with 1-carbometh- 
oxy-yS-carboline ( VIII) , which has been formerly found in Pleiocarpa rrmtica 
Benth. (Apocynaceae) {34) . 



398 




(™) 

A /3-carboline alkaloid with a more elaborated, novel type of structure, 
was isolated also in our laboratory by Brauchli et al {35) , from Pogonopus 
tuhuloms (DC) Schum. a Kubiaceae which grows in the Central and 
Northern part of Argentina, where in some places it is employed against 
fever. The base was named tubulosine (IX), and is structurally related to 
emetine (X) the tetrahydroisoquinoline moiety of the latter alkaloid being 
replaced by a /3-carboline. Bases with this typical skeleton have been latter 
identified in Alangmm lamarckii Thw. (Alangiaceae) (36) and in Gas- 
sinopsis Uicifolia'Kmitze (Icacinaceae) (37). 

It is of interest to note that besides P. harmala, the typical ;8-carbolines 
present in the Banisteriopsis species, have been isolated from a few species 
indigenous to other continents. In an African Rubiaceae, Leptactine densi- 
flora Hook ( ± ) -tetrahydroharmine (leptaflorine) (III) have been found 
(38). Passiflora incarnata L. and possible other Passiflora species (Passi- 
floraceae) {39)., contain harmine (I), which has also been found in Zygo- 
pKyllwrn fabago., {JiB). 

Other simple /3-carbolines closely related in structure to the Baniste- 
riopsis alkaloids have been isolated from other plants. They are listed in 
Table I with an indication of the source of isolation. 

Many of the species containing /3-carboline alkaloids have been used in 
popular medicine and several of the bases isolated have been submitted to 
pharmacological studies, and a few of them even employed in therapeutics. 
But outside America, so far as I know, plants containing those alkaloids have 
not been employed for their hallucinogenic properties. 



399 




(i) (a) NiEDENzu, F. in A. Engler and K. Prandl, Die Naturlichen Pflanzenfamilien, 
III, 4 : 41-74. Leipzig, W. Engelmann, 1896. ( 6 ) Niedenzu, F. in A. Engler, Das 
Pflanzenreich, IV, 141. Leipzig, W. Engelmann, 1928. (c) O'Donell, C. A., and 
A. LouETEiG. Malpighiaeeae Argentlnae. Lilloa, 9 : 221-316, 1943. (d) Pereika, E., 
Contribugao ao Conhecimento da familia Malpighiaeeae. Arquiv. Servic. Forestal 
(Rio de Janeiro). 7: 11-70, 1953. (e) Cuateecasas, J., Prima flora Colombiana. 
Webbia, 13 : 343-664, 1957/1958. 

(2-) Peeeot, E., and Ratmond-Hamet. "Yage, Ayahuasca, Caapi et leur alcaloide: tele- 
pathine ou yageine." Bull. Scienc. Pharmacol., 34: 337-347, 417-^6, 500-514, 
1927. 

(3) Rios, O. "Aspectos preliminares al estudio Farmaco-Psiquiatrico del Ayahuasca y 
su Principio Activo." Anales Fac. Med. Univ. Nacl. Mayor San Marcos, Lima. 
45 : 22-66 (1962). Chem. Abstr. 59 : 3215, 1963. 

i4) Zeeda Baeeon, B. Quoted by E. Perrot and Raymond-Hamet in reference (2) and 
by O. Rios and reference (3) . 

(5) Fischee CAedenas G. "Estudio sobre el principio activo del Yage." Thesis, Fac. 

Medic. Cienc. Natural. Bogota, 1923. Quoted by E. Perrot and Raymond-Hamet in 
reference (2) and by O. Rios in reference (3) . 

(6) Baeeiga Vn.T.AT.BA, A. M. "Yajeine. A new alkaloid." J. Soc. Chem. Ind. 44 : 205- 

207, 1925. 

(7) Baeeiga Villalba, A. M. El yage. Bebida especial de los indios riberenos del Putu- 

mayo y el Amazonas." Bol. Lab. Semper-Martinez, N" espec. 9, 1927. Quoted by 
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(8) ScHtTLTES, R. E., and R. F. Raffauf. "Prestonia: An Amazon narcotic or not" 

Bot. Museum Leafl. Harvard Univ., 19 : 109-122, 1960. 

(9) Lewin, L. "Sur une substance enivrante, la banlsterine, extraite de Banisteria 

caapi." Compt. Rend., 186 : 469-471, 1928. 
(10) Elgee, F. "Ueber das Vorkommen von Harmin in einer siidamerikanischen Liane 
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400 



(11) Wolfe, O., and K. Rumpf. "Ueber die gewinnung von Hamin aus einer siidameri- 

kanischen Liane." Arch. Pharm., 266 : 188-189, 1928. 

(12) Chen, A. L., and K. K. Chen. "Harmine, The Alkaloid of Caapi." Quart. J. Pharm. 

Pharmacol., 12 : 30-38, 1939. 

(13) HocHSTEiN, F. A., and A. M. Paradies. "Alkaloids from Banisteria caapi and Pres- 

tonia amazonicum." J. Am. Chem. Soc, 79 : 5735-5736, 1957. 
(H) Manske, R. H. F., W. H. Perkin, and R. Robinson. "A synthesis of harmaline." 
J. Chem. Soc., 1-14, 1927. 

(15) KoBLicovA, Z., and J. Trojanek. "The Absolute Configuration of ( + )-l,2,3,4- 

Tetrahydroharmine." Chem. Ind. (London) 1342,1966. 

(16) O'Connell, F. D., and E. V. Lynn. "The Alkaloid of Bamsteriopsis inebrians Mor- 

ton." J. Am. Pharm. Assoc., 42 : 753-754, 1953. 

(17) Poisson, J. "Note sur le 'Natem' boisson toxique peruvienne et ses alcaloides." 

Ann. Pharm. Franc, 23 : 241-244, 1965. 

(18) Raffauf, R. F., and M. B. Flagler. Alkaloids of the Apocynaceae. Econ. Botany, 

14: 37-55 (1960). 

(19) Deulofeu, V. "Chemical Asi)ects of American Medicinal Plants." Lecture, III 

Internat. Pharmacol. Congress. Sao Paulo, Brazil, July 24-30, 1966. 

(20) Wassen, S. H., and B. Holmstedt. "The use of paricft, an ethnological and Phar- 

macological review." Ethnos, 5-45, 1963. Holmstedt, B., Tryptamine derivatives 
in epena, an intoxicating snufC used by some South American Indian tribes. Arch. 
Intern. Pharmacodyn., 156 : 285-305, 1965. 

(21) (a) ScHULTES, R. E. "The identity of the Malpighiaceous narcotics of South 

America." Bot. Museum Leafl. Harvard Univ., 18: 1-56, j.<,57. (b) Schultes, E. R. 
"Botanical Sources of the New World Narcotics." Psychedelic Rev., 1 : 145-166, 
1963. (c) Schultes, R. E. "Ein halbes Jahrhundert Ethnobotanik amerikanischer 
Halluzinogene." Planta Medica, 13 : 125-157, 1965. 

(22) Webb, L. J. Australian Phytochemical Survey. Part I, Bulletin 241. Melbourne, 

CSIRO, 1949. pag. 34. 

(23) Unpublished results from our Laboratory. 

(24) Mors, W. B., and P. Zaltzman. "Sobre o alcaloide da Banisteria caapi Spruce e 

do Cabi Paraensise Ducke." Bol. inst. quim. agr. (Rio de Janeiro) N° 34: 17-27, 
1954. Chem. Abstr., 49, 14906, 1955. 

( 25 ) Quoted by Mors and Zaltzman in reference 24. 

(26) RiBEiRo, O., and A. Machado. Lophanterine, a new alkaloid. Anais assoc. quim. 

Brasil, 5 : 39-42, 1946. Chem. Abstr., 41, 3109, 1947. 

(27) BioccA, E. C. Galeffi, E. G. Montalvo, and G. B. Marini-Bettolo. "SuUe sostanze 

allucinogene impiegate in Amazonia. Nota I. Osservazioni sul Parica dei Tukano 
e Tariana del bacino del Rio Uaupes." Ann. Chim. (Roma), 54: 117.5-1178, 1964. 

(28) Bebnhauer, K. "Notiz ueber die Isolierung von Harmin und (-f)-l,2,3,4-Tetrahy- 

dro-harmin aus einer indianischen Schupfdroge." Helv. Chim. Acta., 47; 1075- 
1077, 1964. 

(29) Marini-Bettolo, G. B., F. Delle Monaohe, and E. Biocca. "SuUe sostanze alluci- 

nogene impiegate in Amazonia. Nota II. Osservazioni sull'Epena degli Yanoama 
del bacino del Rio Negro e dan'Alto Orinoco." Ann. Chim. (Roma), 54: 1179- 
1186, 1964. 

(30) Stowe, B. R. "Occurrence and Metabolism of Simple Indoles in Plants." Prog. 

Chem. Org. Nat. Prod., 17 : 248-297, 1959. Saxton, J. E. The Simple Bases. In 
R.H.F. Manske, The Alkaloids, Vol. 8 : 1-25. New York, Academic Press, 1965. 

(31) Baohli, E., C. Vamvacas, H. Schmid, and P. Karrer. "Uber die Alkaloide aus der 

Rinde von Strychnos melinoniana Baillon." Helv. Chim. Acta, 40: 1167-1187, 
1957. 

(32) Antonaccio, L. D., and H. Budzikiewicz. "Harman-3-carbonsaure ein neues Al- 

kaloid aus Aspidosperma polyneuron." Monatsh. Chem., 93 : 962-964, 1962. 

(33) Sanchez E. and J. Oomin. Unpublished results. 



401 



(3^) AcHENBACH, H., and K. Biemann. "Isotiiboflavine and Norisotuboflavine. Two new- 
Alkaloids Isolated from Pleiocarpa mutica." J. Am. Ohem. Soc, 87 : 4177-^81, 
1965. 

(55) Beattohli, p., V. Deulofeu, H. Bubzikiewicz, and C. Djerassi. "The Structure 
of Tubulosine, a Novel Alkaloid from Pogonopus tuiulosus (DC.) Schumann." 
J. Am. Chem. Soc., 86 : 1895-1896, 1964. 

(36) Pakrashi, S. O. "Indian Medicinal Plants XI. A new Alkaloid from the root bark 

of Alangium Jamarckii." Indian J. Ohem., 2 : 468, 1964. 

(37) MoNTEiEO, H., H. BuDziKiEwicz, C. Djeeassi, R. R. Akdt, and W. H. Baarschebs. 

"Structure of Deoxytubulosine and interconversion with Tubulosine." Chem. 
Comm., 317-318, 1965. 

(38) Paris, R. B., F. Pebchebon, J. Mainil, and R. Goutabel. "Alcaloldes du Leptac- 

tina densiflora Hook." f. Bull. Soc. Ohim. France, 780-782, 1957. 
(35) Neu, R. "Inhaltssoffe der Passiflora iticarnata. 3. Mitt." Arzneimittel-Forsch., 6: 
94^99, 1956. 

(40) Ltttomski, L. "Isolation of the major alkaloids from Passiflora incarnata L." Biul. 

Inst. RoSUn Leczniczych. 6 : 20^219, 1960. Chem. Abstr., 55 : 21479, 1961. 
{41) HuLTiN, E. "Partition coefficients of ether extractable passionflower alkaloids." 

Acta Chem. Scand., 19 : 1431-1434, 1965. 

(42) Abdusalamoy, B., A. S. Sadtkov, and Kh. A. Aslanov. "Alkaloids and aminoacids 

of CalUgonum." Nauchn. Tr. Tashkentsk. Gos. Univ., N° 263 : 3-7, 1964. Chem. 
Abstr., 63 : 3314, 1965. 

(43) Platonova, T. F., a D. Ktjzotkov, and P. S. Massagetov. "Alkaloids of Chenopo- 

diaceae: Anaiasis jaxartica and Arthrophytum leptocladum." Zhur. Obshchei 
Khim., 28 : 3128-3131, 1958. Chem. Abstr., 53 : 7506, 1959. 

(44) Badgee, G. M., and A. F. Beecham. "Isolation of Tetrahydroharman from Petalo- 

styles laiicheoides." Nature (London), 168 : 517, 1951. 

(45) Men'shikov, G. p., E. L. Gubevich, and G. A. Samsonova. "Alkaloids of Elaeagnus 

angusHfolia. Structure of eleagnine." Zhur. Obshchei Khim., 20: 1927-1928, 
1950. Chem. Abstr., 45 : 2490, 1951. 

(46) Oeazkuuev, I. K., O. S. Ostboshexko, and A. S. Sadtkov. "An adsorption method 

for the separation of alkaloids of Hammada leptoclOrda." Zhur. Prikl. Khim., 37 : 
1394-1395, 1964. Chem. Abstr., 61 : 11014, 1964. 

(47) Johns, S. R., J. A. Lambebton, and A. A. Sioumis. "Alkaloids of the Australian 

Leguminosae VII.A^s-Methyltetrahydroharman from Acacia complnnata." Aus- 
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(48) BoBKOwsKi, B. "Chromatographic determination of alkaloids of Zygophyllum 

faiago." Biul. Inst. RoSlin Leczniczych. 5 : 158-168, 1959. Chem. Abstr., 54 : 
15844, 1960. 

(49) Platon'ova, T. F., a. D. Kuzovkov, and P. S. Massagetov. "Alkaloids of plants of 

the Elaeagnaceae family. Isolation of tetrahydroharmol and X-methyl-tetrahy- 
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1957. 



402 



SESSION VI 



AMANITA MUSCARIA (FLY AGARIC) 

Daniel H. Efron, Chairman 



Fly Agaric and Man 



R. Gordon Wasson 

Botanical Museum of Harvard University 
Cambridge, Massachusetts 

For the past three or four years I have devoted some of my time to the 
quest for information about the fly agaric, as this mushroom is called in 
England, Amanita muscaria Fr. as it is known to mycologists, and especially 
concerning its historic role in the Eurasian cultures, where its use as an 
inebriant has survived down to recent times. The results of my inquiries 
have led me to write a book on the subject, which is almost ready for the 
printer. Today it is my privilege to lay before you some of my findings and 
conclusions. 

My theme has surprising ramifications, as I think you will agree when I 
have done. Indologists will review my evidence, but if I am right, it will 
be necessary for us all to make room in our own remote past for the part 
played by this mushroom, and the fly agaric will take its place by the side 
of alcohol, hashish, and tobacco as an outstanding inebriant utilized by Homo 
sapiem living in Eurasia. 

The documented history of this inebriant goes back only to the l7th cen- 
tury and is confined to the northern reaches of Siberia. That its unwritten 
history begins earlier is certain, but how much earlier and how widespread 
its use was, are questions that remain to be answered. So far as I can learn, 
my inquiries mark the first fumbling effort to arrive at those answers. 

The intellectual element in Europe learned for the first time of the fly 
agaric as an inebriant in 1730, when Philip John von Strahlenberg, a Swedish 
army officer, published in Stockholm a book written in German on the twelve 
years he had spent as a prisoner of the Russians in Siberia. This work, trans- 
lated into English, came out in London in two printings, in 1736 and 1738, 
under a lengthy title beginning An Historico-GeographicaZ Description of 
the North and Eastern Parts of Europe and Asia (1). Somewhat earlier, in 
1658, a Polish prisoner in Siberia had observed the fly agaric being consumed 
for its inebriating effect by the Ostyak (or Khanty) in the valley of the 
Irtysh, a tributary of the Ob in western Siberia ; but his diary was not pub- 
lished until 1874 (2) . The first Eussian to record the practice seems to have 
been Stepan Petrovich Krasheninnikov in 1755 (S), who, like von Strahlen- 
berg, was writing about the Koryak, in the extreme Orient. Since their time 
more than a score of observers have given us accounts of this curious custom. 
They have included Russian anthropologists, linguists (many of these Hun- 
garian or Finnish), and a varied assortment of travelers and adventurers, 
some of whom are remarkably superficial and supercilious. In my forthcom- 
ing book I am planning to publish in extenso, in English, what these men 
have had to say about the consumption of the fly agaric in Siberia. In addi- 
tion to these primary sources, whether good or bad, there are a number of 
serious writers who have concerned themselves with the problem : the phar- 



405 



macologists Ernst von Bibra (^), C. Hartwich (S), and Louis Lewin (6) — 
all German — and the Frenchman Philipe de Felice (7), the Swede Ake 
Ohlmarks (8), and the Hungarian J. Balazs (9). In addition, there have 
been innumerable literary allusions traceable to the marvelous properties of 
the fly agaric. One need only mention as examples, in English, Oliver Gold- 
smith in his Letters from a Citizen of the World (No. 32), an immensely 
popular book in the 18th century, and the celebrated mushroom in Alice in 
Wonderland. 

The Distribution of the Practice 

We possess reliable testimony permitting us to say that in recent centuries 
there have been two foci where the fly agaric has been used as an inebriant. 

1. In the Ob Valley, in the extreme west of Siberia,